1-167021755-A-G

Position:

chr1-167021755-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032858.3(MAEL):c.1205A>G(p.Asn402Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,613,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

MAEL
NM_032858.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.26

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033992708).

BP6

Variant 1-167021755-A-G is Benign according to our data. Variant chr1-167021755-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2400851.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAEL	NM_032858.3 linkuse as main transcript	c.1205A>G	p.Asn402Ser	missense_variant	12/12	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.1205A>G	p.Asn402Ser	missense_variant	12/12	1	NM_032858.3	ENSP00000356846	P1	Q96JY0-1
MAEL	ENST00000367870.6 linkuse as main transcript	c.1112A>G	p.Asn371Ser	missense_variant	11/11	1		ENSP00000356844		Q96JY0-2
MAEL	ENST00000622874.4 linkuse as main transcript	c.1037A>G	p.Asn346Ser	missense_variant	13/13	1		ENSP00000482771
MAEL	ENST00000491055.5 linkuse as main transcript	n.1896A>G		non_coding_transcript_exon_variant	12/12	1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000757

AC:

AN:

251012

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000732

AC:

107

AN:

1461194

Hom.:

Cov.:

AF XY:

0.0000812

AC XY:

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000855

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000970

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.098

DANN

Benign

0.55

DEOGEN2

Benign

0.028

.;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.22

.;N;N

REVEL

Benign

0.095

Sift

Benign

0.51

.;T;T

Sift4G

Benign

0.59

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.11

MVP

0.19

MPC

0.14

ClinPred

0.017

GERP RS

-8.5

Varity_R

0.031

gMVP

0.095

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