6-10762764-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001242957.3(MAK):c.*1688C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,624 control chromosomes in the GnomAD database, including 53,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.83 (53012 hom., cov: 32)
  • Exomes 𝑓: 0.84 (151 hom.)
• Consequence: MAK NM_001242957.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.54

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-10762764-G-T is Benign according to our data. Variant chr6-10762764-G-T is described in ClinVar as [Benign]. Clinvar id is 354768.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAK	NM_001242957.3	c.*1688C>A		3_prime_UTR_variant	15/15	ENST00000354489.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAK	ENST00000354489.7	c.*1688C>A		3_prime_UTR_variant	15/15	5	NM_001242957.3	P4

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126444 AN: 152074 Hom.: 52966 Cov.: 32

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.800

GnomAD4 exome AF: 0.843 AC: 364 AN: 432 Hom.: 151 Cov.: 0 AF XY: 0.867 AC XY: 222 AN XY: 256

Gnomad4 FIN exome AF: 0.841

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.832 AC: 126553 AN: 152192 Hom.: 53012 Cov.: 32 AF XY: 0.834 AC XY: 62071 AN XY: 74424

Gnomad4 AFR AF: 0.934

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.920

Gnomad4 SAS AF: 0.816

Gnomad4 FIN AF: 0.870

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.797

Alfa AF: 0.781 Hom.: 62056

Bravo AF: 0.831

Asia WGS AF: 0.865 AC: 3005 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis Pigmentosa, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	8.3
Dann	Benign	0.63

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: rs501948; hg19: chr6-10762997;