Genetic Variant TMEM41A:p.Ala49Gly (chr3-185496955-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080652.4(TMEM41A):c.146C>G(p.Ala49Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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. A49V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMEM41A
NM_080652.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.50

Publications

0 publications found

Variant links:

Genes affected

TMEM41A (HGNC:30544): (transmembrane protein 41A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM41A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20049661).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080652.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM41A	NM_080652.4	MANE Select	c.146C>G	p.Ala49Gly	missense	Exon 2 of 5	NP_542383.1	Q96HV5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM41A	ENST00000421852.6	TSL:1 MANE Select	c.146C>G	p.Ala49Gly	missense	Exon 2 of 5	ENSP00000406885.1	Q96HV5
TMEM41A	ENST00000856958.1		c.146C>G	p.Ala49Gly	missense	Exon 2 of 4	ENSP00000527017.1
TMEM41A	ENST00000296254.3	TSL:2	c.146C>G	p.Ala49Gly	missense	Exon 2 of 3	ENSP00000296254.3	H7BXL1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

221294

AF XY:

0.00

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 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:

1446466

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717924

African (AFR)

AF:

0.00

AC:

AN:

33394

American (AMR)

AF:

0.00

AC:

AN:

41646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25640

East Asian (EAS)

AF:

0.00

AC:

AN:

39272

South Asian (SAS)

AF:

0.00

AC:

AN:

83228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5346

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106084

Other (OTH)

AF:

0.00

AC:

AN:

59934

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

M_CAP

Benign

0.0082

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.6

PhyloP100

5.5

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.77

REVEL

Benign

0.064

Sift

Uncertain

0.023

Sift4G

Benign

0.074

Polyphen

0.0090

Vest4

0.27

MutPred

0.33

Gain of glycosylation at S46 (P = 0.0332)

MVP

0.13

MPC

0.21

ClinPred

0.88

GERP RS

4.5

Varity_R

0.092

gMVP

0.30

Mutation Taster

=78/22

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over