rs76319365

Variant names:

• chr10-69010950-G-A
• rs76319365
• NM_015634.4:c.925G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-69010950-G-A
• chr10-69010950-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015634.4(KIFBP):​c.925G>A​(p.Glu309Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIFBP NM_015634.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.45
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFBP	NM_015634.4	c.925G>A	p.Glu309Lys	missense_variant	Exon 6 of 7	ENST00000361983.7	NP_056449.1
KIFBP	XM_017016067.2	c.127G>A	p.Glu43Lys	missense_variant	Exon 3 of 4		XP_016871556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFBP	ENST00000361983.7	c.925G>A	p.Glu309Lys	missense_variant	Exon 6 of 7	1	NM_015634.4	ENSP00000354848.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Goldberg-Shprintzen syndrome Uncertain:1

Mar 04, 2013

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.0	M;.
PhyloP100		8.4
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Uncertain	0.34
Sift	Uncertain	0.016	D;.
Sift4G	Benign	0.096	T;.
Polyphen		0.96	D;.
Vest4		0.86
MutPred		0.45		Gain of MoRF binding (P = 0.0076);.;
MVP		0.68
MPC		1.2
ClinPred		0.95	D
GERP RS		5.4
Varity_R		0.52
gMVP		0.66
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs76319365; hg19: chr10-70770706;