chr6-10764456-C-G

Variant names:

• chr6-10764456-C-G
• rs767273634
• NM_001242957.3:c.1943G>C

Variant summary

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

The NM_001242957.3(MAK):​c.1943G>C​(p.Arg648Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAK NM_001242957.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.94

Genes affected

MAK (HGNC:6816): (male germ cell associated kinase) The product of this gene is a serine/threonine protein kinase related to kinases involved in cell cycle regulation. Studies of the mouse and rat homologs have localized the kinase to the chromosomes during meiosis in spermatogenesis, specifically to the synaptonemal complex that exists while homologous chromosomes are paired. Mutations in this gene have been associated with ciliary defects resulting in retinitis pigmentosa 62. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TMEM14B (HGNC:21384): (transmembrane protein 14B) Enables identical protein binding activity. Involved in cerebral cortex development; neural precursor cell proliferation; and regulation of G1/S transition of mitotic cell cycle. Predicted to be integral component of membrane. Predicted to be active in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272162 (HGNC:):

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
MAK	NM_001242957.3	c.1943G>C	p.Arg648Pro	missense_variant	Exon 15 of 15	ENST00000354489.7	NP_001229886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAK	ENST00000354489.7	c.1943G>C	p.Arg648Pro	missense_variant	Exon 15 of 15	5	NM_001242957.3	ENSP00000346484.3
ENSG00000272162	ENST00000480294.1	n.100+14758C>G		intron_variant	Intron 3 of 18	2		ENSP00000417929.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251062 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135766

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Pathogenic	0.17
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;T;.;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	.;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Uncertain	2.3	M;M;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.8	D;.;.;.
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	D;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.95	P;P;.;.
Vest4		0.64
MutPred		0.41		Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);.;.;
MVP		0.88
MPC		0.82
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.85
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs767273634; hg19: chr6-10764689;