chr10-69016203-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015634.4(KIFBP):c.1653C>T(p.Ala551Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 1,612,732 control chromosomes in the GnomAD database, including 3,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 235 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3392 hom. )

Consequence

KIFBP
NM_015634.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0810

Publications

8 publications found

Variant links:

Genes affected

KIFBP (HGNC:23419): (kinesin family binding protein) This gene encodes a kinesin family member 1 binding protein that is characterized by two tetratrico peptide repeats. The encoded protein localizes to the mitochondria and may be involved in regulating transport of the mitochondria. Mutations in this gene are associated with Goldberg-Shprintzen megacolon syndrome. [provided by RefSeq, Mar 2010]

KIFBP Gene-Disease associations (from GenCC):

Goldberg-Shprintzen syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

KIFBP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 10-69016203-C-T is Benign according to our data. Variant chr10-69016203-C-T is described in ClinVar as Benign. ClinVar VariationId is 158694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.081 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFBP	NM_015634.4 link	c.1653C>T	p.Ala551Ala	synonymous_variant	Exon 7 of 7	ENST00000361983.7	NP_056449.1
KIFBP	XM_017016067.2 link	c.855C>T	p.Ala285Ala	synonymous_variant	Exon 4 of 4		XP_016871556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFBP	ENST00000361983.7 link	c.1653C>T	p.Ala551Ala	synonymous_variant	Exon 7 of 7	1	NM_015634.4	ENSP00000354848.4		Q96EK5

Frequencies

GnomAD3 genomes

AF:

0.0495

AC:

7526

AN:

152092

Hom.:

236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0133

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0661

Gnomad ASJ

AF:

0.0994

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0195

Gnomad FIN

AF:

0.0258

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0735

Gnomad OTH

AF:

0.0771

GnomAD2 exomes

AF:

0.0504

AC:

12615

AN:

250286

AF XY:

0.0513

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.0448

Gnomad ASJ exome

AF:

0.0996

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0296

Gnomad NFE exome

AF:

0.0722

Gnomad OTH exome

AF:

0.0677

GnomAD4 exome

AF:

0.0644

AC:

94058

AN:

1460522

Hom.:

3392

Cov.:

AF XY:

0.0633

AC XY:

45980

AN XY:

726462

show subpopulations

African (AFR)

AF:

0.0117

AC:

390

AN:

33390

American (AMR)

AF:

0.0473

AC:

2104

AN:

44528

Ashkenazi Jewish (ASJ)

AF:

0.0968

AC:

2525

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0218

AC:

1876

AN:

86004

European-Finnish (FIN)

AF:

0.0302

AC:

1615

AN:

53406

Middle Eastern (MID)

AF:

0.120

AC:

692

AN:

5756

European-Non Finnish (NFE)

AF:

0.0727

AC:

80847

AN:

1111354

Other (OTH)

AF:

0.0665

AC:

4009

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

4924

9848

14771

19695

24619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2890

5780

8670

11560

14450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0494

AC:

7515

AN:

152210

Hom.:

235

Cov.:

AF XY:

0.0468

AC XY:

3485

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0133

AC:

552

AN:

41530

American (AMR)

AF:

0.0659

AC:

1007

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0994

AC:

345

AN:

3470

East Asian (EAS)

AF:

0.000192

AC:

AN:

5196

South Asian (SAS)

AF:

0.0193

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0258

AC:

273

AN:

10590

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0735

AC:

4998

AN:

68014

Other (OTH)

AF:

0.0768

AC:

162

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

368

736

1104

1472

1840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0582

Hom.:

226

Bravo

AF:

0.0515

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0880

EpiControl

AF:

0.0856

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 23, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Goldberg-Shprintzen syndrome

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

May 07, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.4

(source)

DANN

Benign

0.64

PhyloP100

-0.081

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over