6-10763850-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001242957.3(MAK):c.*601_*602insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (33299 hom., cov: 0)
  • Exomes 𝑓: 0.18 (0 hom.)
• Consequence: MAK NM_001242957.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.957

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 -10 ACMG points.

• BP6: Variant 6-10763850-C-CA is Benign according to our data. Variant chr6-10763850-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 354777.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAK	NM_001242957.3	c.*601_*602insT		3_prime_UTR_variant	15/15	ENST00000354489.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAK	ENST00000354489.7	c.*601_*602insT		3_prime_UTR_variant	15/15	5	NM_001242957.3	P4

Frequencies

GnomAD3 genomes AF: 0.693 AC: 95248 AN: 137476 Hom.: 33317 Cov.: 0

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.693

GnomAD4 exome AF: 0.182 AC: 8 AN: 44 Hom.: 0 Cov.: 0 AF XY: 0.179 AC XY: 5 AN XY: 28

Gnomad4 AMR exome AF: 0.125

Gnomad4 SAS exome AF: 0.100

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.693 AC: 95221 AN: 137490 Hom.: 33299 Cov.: 0 AF XY: 0.697 AC XY: 46146 AN XY: 66242

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.906

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.692

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis Pigmentosa, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs60516370; hg19: chr6-10764083;