Genetic Variant MAK:c.*1373C>T (chr6-10763079-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.333

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MAK	NM_001242957.3 link	c.*1373C>T		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.*1373C>T		3_prime_UTR_variant	Exon 15 of 15	5	NM_001242957.3	ENSP00000346484.3		P20794-2
ENSG00000272162	ENST00000480294.1 link	n.100+13381G>A		intron_variant	Intron 3 of 18	2		ENSP00000417929.1		F8WBI7

Frequencies

GnomAD3 genomes

AF:

0.778

AC:

118366

AN:

152068

Hom.:

46186

Cov.:

show subpopulations

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.:

AF XY:

0.865

AC XY:

225

AN XY:

260

show subpopulations

Gnomad4 AFR exome

AC:

AN:

Gnomad4 AMR exome

AF:

1.00

AC:

AN:

Gnomad4 ASJ exome

AC:

AN:

Gnomad4 EAS exome

AC:

AN:

Gnomad4 SAS exome

AC:

AN:

Gnomad4 FIN exome

AF:

0.840

AC:

358

AN:

426

Gnomad4 NFE exome

AF:

0.500

AC:

AN:

Gnomad4 Remaining exome

AF:

1.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.778

AC:

118450

AN:

152186

Hom.:

46215

Cov.:

AF XY:

0.783

AC XY:

58243

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.755

AC:

0.754616

AN:

0.754616

Gnomad4 AMR

AF:

0.753

AC:

0.753338

AN:

0.753338

Gnomad4 ASJ

AF:

0.712

AC:

0.711982

AN:

0.711982

Gnomad4 EAS

AF:

0.919

AC:

0.91882

AN:

0.91882

Gnomad4 SAS

AF:

0.815

AC:

0.814623

AN:

0.814623

Gnomad4 FIN

AF:

0.869

AC:

0.86863

AN:

0.86863

Gnomad4 NFE

AF:

0.775

AC:

0.77539

AN:

0.77539

Gnomad4 OTH

AF:

0.761

AC:

0.76089

AN:

0.76089

Heterozygous variant carriers

1378

2756

4135

5513

6891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.769

Hom.:

122576

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

LINK: link

Submissions by phenotype

Retinitis Pigmentosa, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.3

DANN

Benign

0.55

Mutation Taster

=100/0

polymorphism (auto)

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over