6-10763079-G-A

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.*1373C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,620 control chromosomes in the GnomAD database, including 46,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.78 (46215 hom., cov: 33)
  • 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: 0.333

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=-0.66).
• BP6: Variant 6-10763079-G-A is Benign according to our data. Variant chr6-10763079-G-A is described in ClinVar as [Benign]. Clinvar id is 354772.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAK	NM_001242957.3	c.*1373C>T		3_prime_UTR_variant	15/15	ENST00000354489.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAK	ENST00000354489.7	c.*1373C>T		3_prime_UTR_variant	15/15	5	NM_001242957.3	P4

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118366 AN: 152068 Hom.: 46186 Cov.: 33

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.763

GnomAD4 exome AF: 0.841 AC: 365 AN: 434 Hom.: 151 Cov.: 0 AF XY: 0.865 AC XY: 225 AN XY: 260

Gnomad4 AMR exome AF: 1.00

Gnomad4 FIN exome AF: 0.840

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.778 AC: 118450 AN: 152186 Hom.: 46215 Cov.: 33 AF XY: 0.783 AC XY: 58243 AN XY: 74406

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.919

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.761

Alfa AF: 0.767 Hom.: 71911

Bravo AF: 0.771

Asia WGS AF: 0.849 AC: 2950 AN: 3478

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	1.3
Dann	Benign	0.55

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: rs526495; hg19: chr6-10763312;