Genetic Variant MAK:c.*312dupA (chr6-10764139-G-GT) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The NM_001242957.3(MAK):c.*312dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00701 in 258,468 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.016 ( 0 hom. )

Consequence

MAK
NM_001242957.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0770

Variant links:

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]

MAK links:

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]

TMEM14B links:

ENSG00000272162 (HGNC:):

ENSG00000272162 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0165 (1769/107456) while in subpopulation MID AF= 0.0243 (11/452). AF 95% confidence interval is 0.0179. There are 0 homozygotes in gnomad4_exome. There are 955 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAK	NM_001242957.3 link	c.*312dupA		3_prime_UTR_variant	Exon 15 of 15	ENST00000354489.7	NP_001229886.1	P20794-2F8VBW7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAK	ENST00000354489 link	c.*312dupA		3_prime_UTR_variant	Exon 15 of 15	5	NM_001242957.3	ENSP00000346484.3		P20794-2
ENSG00000272162	ENST00000480294.1 link	n.100+14450dupT		intron_variant	Intron 3 of 18	2		ENSP00000417929.1		F8WBI7

Frequencies

GnomAD3 genomes

AF:

0.000285

AC:

AN:

150910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000390

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000264

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.0000970

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000295

Gnomad OTH

AF:

0.000483

GnomAD4 exome

AF:

0.0165

AC:

1769

AN:

107456

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

955

AN XY:

56168

show subpopulations

Gnomad4 AFR exome

AF:

0.0224

Gnomad4 AMR exome

AF:

0.0151

Gnomad4 ASJ exome

AF:

0.0162

Gnomad4 EAS exome

AF:

0.0171

Gnomad4 SAS exome

AF:

0.0116

Gnomad4 FIN exome

AF:

0.0138

Gnomad4 NFE exome

AF:

0.0172

Gnomad4 OTH exome

AF:

0.0171

GnomAD4 genome

AF:

0.000285

AC:

AN:

151012

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

AN XY:

73758

show subpopulations

Gnomad4 AFR

AF:

0.000389

Gnomad4 AMR

AF:

0.000264

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.0000970

Gnomad4 NFE

AF:

0.000295

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.000355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over