Variant 1-166992758-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000367872.9(MAEL):c.398G>A(p.Arg133His) variant causes a missense change. The variant allele was found at a frequency of 0.00449 in 1,611,256 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 14 hom. )

Consequence

MAEL
ENST00000367872.9 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.89

Variant links:

Genes affected

MAEL (HGNC:25929): (maelstrom spermatogenic transposon silencer) Predicted to enable sequence-specific DNA binding activity. Predicted to be involved in gamete generation; negative regulation of macromolecule metabolic process; and piRNA metabolic process. Predicted to act upstream of or within several processes, including homologous chromosome pairing at meiosis; intrinsic apoptotic signaling pathway in response to DNA damage; and negative regulation of macromolecule metabolic process. Predicted to be located in piP-body. Predicted to be active in P granule and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MAEL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010195971).

BP6

Variant 1-166992758-G-A is Benign according to our data. Variant chr1-166992758-G-A is described in ClinVar as [Benign]. Clinvar id is 777103.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAEL	NM_032858.3 linkuse as main transcript	c.398G>A	p.Arg133His	missense_variant	4/12	ENST00000367872.9	NP_116247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAEL	ENST00000367872.9 linkuse as main transcript	c.398G>A	p.Arg133His	missense_variant	4/12	1	NM_032858.3	ENSP00000356846	P1	Q96JY0-1

Frequencies

GnomAD3 genomes

AF:

0.00342

AC:

519

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00909

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00516

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00328

AC:

815

AN:

248852

Hom.:

AF XY:

0.00334

AC XY:

449

AN XY:

134554

show subpopulations

Gnomad AFR exome

AF:

0.000743

Gnomad AMR exome

AF:

0.000820

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000334

Gnomad FIN exome

AF:

0.00904

Gnomad NFE exome

AF:

0.00489

Gnomad OTH exome

AF:

0.00280

GnomAD4 exome

AF:

0.00461

AC:

6720

AN:

1459178

Hom.:

Cov.:

AF XY:

0.00454

AC XY:

3296

AN XY:

725844

show subpopulations

Gnomad4 AFR exome

AF:

0.000690

Gnomad4 AMR exome

AF:

0.000700

Gnomad4 ASJ exome

AF:

0.0000767

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000397

Gnomad4 FIN exome

AF:

0.00919

Gnomad4 NFE exome

AF:

0.00537

Gnomad4 OTH exome

AF:

0.00294

GnomAD4 genome

AF:

0.00341

AC:

519

AN:

152078

Hom.:

Cov.:

AF XY:

0.00348

AC XY:

259

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00138

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00909

Gnomad4 NFE

AF:

0.00516

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00410

Hom.:

Bravo

AF:

0.00257

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.00335

AC:

407

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

.;.;T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.010

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.97

.;.;L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.2

.;N;N;N

REVEL

Benign

0.24

Sift

Uncertain

0.016

.;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

.;.;D;.

Vest4

0.76

MVP

0.76

MPC

0.59

ClinPred

0.0096

GERP RS

5.7

Varity_R

0.20

gMVP

0.73

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