10-68988948-C-T

Variant names:

• chr10-68988948-C-T
• rs372223602
• NM_015634.4:c.116C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015634.4(KIFBP):​c.116C>T​(p.Ala39Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A39G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KIFBP NM_015634.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.53

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 Uncertain_significance. Variant got 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.116C>T	p.Ala39Val	missense_variant	Exon 1 of 7	ENST00000361983.7	NP_056449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFBP	ENST00000361983.7	c.116C>T	p.Ala39Val	missense_variant	Exon 1 of 7	1	NM_015634.4	ENSP00000354848.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.35	T;T;T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Uncertain	-0.027	T
MutationAssessor	Uncertain	2.5	M;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.7	D;.;.
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D;.;.
Sift4G	Uncertain	0.013	D;.;D
Polyphen		1.0	D;.;.
Vest4		0.77
MutPred		0.43		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.79
MPC		1.3
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.74
gMVP		0.83

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: rs372223602; hg19: chr10-70748704;