rs35893997

Positions:

• chr10-69016203-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0810

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 158694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-69016203-C-T is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
KIFBP	NM_015634.4	c.1653C>T	p.Ala551Ala	synonymous_variant	7/7	ENST00000361983.7	NP_056449.1
KIFBP	XM_017016067.2	c.855C>T	p.Ala285Ala	synonymous_variant	4/4		XP_016871556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIFBP	ENST00000361983.7	c.1653C>T	p.Ala551Ala	synonymous_variant	7/7	1	NM_015634.4	ENSP00000354848.4

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7526 AN: 152092 Hom.: 236 Cov.: 32

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

GnomAD3 exomes AF: 0.0504 AC: 12615 AN: 250286 Hom.: 454 AF XY: 0.0513 AC XY: 6943 AN XY: 135288

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 SAS exome AF: 0.0218

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.: 33 AF XY: 0.0633 AC XY: 45980 AN XY: 726462

Gnomad4 AFR exome AF: 0.0117

Gnomad4 AMR exome AF: 0.0473

Gnomad4 ASJ exome AF: 0.0968

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0218

Gnomad4 FIN exome AF: 0.0302

Gnomad4 NFE exome AF: 0.0727

Gnomad4 OTH exome AF: 0.0665

GnomAD4 genome AF: 0.0494 AC: 7515 AN: 152210 Hom.: 235 Cov.: 32 AF XY: 0.0468 AC XY: 3485 AN XY: 74424

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.0659

Gnomad4 ASJ AF: 0.0994

Gnomad4 EAS AF: 0.000192

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.0258

Gnomad4 NFE AF: 0.0735

Gnomad4 OTH AF: 0.0768

Alfa AF: 0.0668 Hom.: 188

Bravo AF: 0.0515

Asia WGS AF: 0.0190 AC: 66 AN: 3478

EpiCase AF: 0.0880

EpiControl AF: 0.0856

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 23, 2016	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. -

Goldberg-Shprintzen syndrome Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.4
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs35893997; hg19: chr10-70775959;