chr10-69000515-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015634.4(KIFBP):c.518T>C(p.Met173Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00786 in 1,584,916 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M173V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0061 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 66 hom. )

Consequence

KIFBP
NM_015634.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 6.47

Publications

10 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008571029).

BP6

Variant 10-69000515-T-C is Benign according to our data. Variant chr10-69000515-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 158697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00605 (922/152336) while in subpopulation NFE AF = 0.00989 (673/68026). AF 95% confidence interval is 0.00927. There are 1 homozygotes in GnomAd4. There are 394 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 66 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015634.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFBP	NM_015634.4	MANE Select	c.518T>C	p.Met173Thr	missense	Exon 2 of 7	NP_056449.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIFBP	ENST00000361983.7	TSL:1 MANE Select	c.518T>C	p.Met173Thr	missense	Exon 2 of 7	ENSP00000354848.4
KIFBP	ENST00000674897.1		c.2T>C	p.Met1?	start_lost	Exon 2 of 7	ENSP00000502225.1
KIFBP	ENST00000638119.2	TSL:5	c.593T>C	p.Met198Thr	missense	Exon 3 of 8	ENSP00000490026.1

Frequencies

GnomAD3 genomes

AF:

0.00606

AC:

923

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00989

Gnomad OTH

AF:

0.00955

GnomAD2 exomes

AF:

0.00650

AC:

1632

AN:

251074

AF XY:

0.00669

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00509

Gnomad ASJ exome

AF:

0.00546

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00246

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00735

GnomAD4 exome

AF:

0.00806

AC:

11542

AN:

1432580

Hom.:

Cov.:

AF XY:

0.00800

AC XY:

5720

AN XY:

714664

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

32868

American (AMR)

AF:

0.00499

AC:

223

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00586

AC:

152

AN:

25928

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39456

South Asian (SAS)

AF:

0.00528

AC:

452

AN:

85674

European-Finnish (FIN)

AF:

0.00308

AC:

164

AN:

53244

Middle Eastern (MID)

AF:

0.00808

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.00917

AC:

9959

AN:

1085658

Other (OTH)

AF:

0.00840

AC:

499

AN:

59392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

522

1044

1567

2089

2611

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.00605

AC:

922

AN:

152336

Hom.:

Cov.:

AF XY:

0.00529

AC XY:

394

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00180

AC:

AN:

41582

American (AMR)

AF:

0.00497

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00540

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00311

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00989

AC:

673

AN:

68026

Other (OTH)

AF:

0.00898

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

147

196

245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00865

Hom.:

Bravo

AF:

0.00578

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00919

AC:

ExAC

AF:

0.00661

AC:

803

Asia WGS

AF:

0.00115

AC:

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (5)

Goldberg-Shprintzen syndrome (1)

KIFBP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.063

Eigen

Benign

-0.059

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0086

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

6.5

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.0

REVEL

Benign

0.13

Sift

Benign

0.71

Sift4G

Benign

0.30

Polyphen

0.16

Vest4

0.77

MVP

0.48

MPC

0.54

ClinPred

0.019

GERP RS

5.1

Varity_R

0.28

gMVP

0.25

Mutation Taster

=78/22

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over