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: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

ACMG classification

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

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFBP	NM_015634.4	MANE Select	c.925G>A	p.Glu309Lys	missense	Exon 6 of 7	NP_056449.1	Q96EK5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFBP	ENST00000361983.7	TSL:1 MANE Select	c.925G>A	p.Glu309Lys	missense	Exon 6 of 7	ENSP00000354848.4	Q96EK5
	KIFBP	ENST00000638119.2	TSL:5	c.1000G>A	p.Glu334Lys	missense	Exon 7 of 8	ENSP00000490026.1	A0A1B0GUA3
	KIFBP	ENST00000674660.1		c.874G>A	p.Glu292Lys	missense	Exon 6 of 7	ENSP00000502562.1	A0A6Q8PH45

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Goldberg-Shprintzen syndrome (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.58	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;