Variant rs11578336 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032858.3(MAEL):c.121T>A(p.Ser41Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S41A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAEL
NM_032858.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.440

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07029942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAEL	NM_032858.3 linkuse as main transcript	c.121T>A	p.Ser41Thr	missense_variant	1/12	ENST00000367872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAEL	ENST00000367872.9 linkuse as main transcript	c.121T>A	p.Ser41Thr	missense_variant	1/12	1	NM_032858.3	P1	Q96JY0-1
MAEL	ENST00000367870.6 linkuse as main transcript	c.121T>A	p.Ser41Thr	missense_variant	1/11	1			Q96JY0-2
MAEL	ENST00000622874.4 linkuse as main transcript	c.-48T>A		5_prime_UTR_variant	2/13	1
MAEL	ENST00000447624.1 linkuse as main transcript	c.121T>A	p.Ser41Thr	missense_variant	1/9	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000499

AC:

AN:

200332

Hom.:

AF XY:

0.00

AC XY:

AN XY:

107154

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000663

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1432326

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709316

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.3

DANN

Benign

0.43

DEOGEN2

Benign

0.022

.;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.079

T;T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.68

N;N;N

REVEL

Benign

0.041

Sift

Benign

0.45

T;T;T

Sift4G

Benign

0.53

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.17

MutPred

0.58

Loss of disorder (P = 0.0721);Loss of disorder (P = 0.0721);Loss of disorder (P = 0.0721);

MVP

0.24

MPC

0.17

ClinPred

0.020

GERP RS

2.5

Varity_R

0.034

gMVP

0.17

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