11-9287776-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015012.4(TMEM41B):​c.493A>G​(p.Met165Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,068 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMEM41B
NM_015012.4 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13
Variant links:
Genes affected
TMEM41B (HGNC:28948): (transmembrane protein 41B) Involved in autophagosome assembly. Located in endoplasmic reticulum membrane and mitochondria-associated endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM41BNM_015012.4 linkc.493A>G p.Met165Val missense_variant Exon 5 of 7 ENST00000528080.6 NP_055827.1 Q5BJD5-1
TMEM41BXM_047426969.1 linkc.500A>G p.Tyr167Cys missense_variant Exon 5 of 6 XP_047282925.1
TMEM41BNR_028491.3 linkn.645A>G non_coding_transcript_exon_variant Exon 5 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM41BENST00000528080.6 linkc.493A>G p.Met165Val missense_variant Exon 5 of 7 1 NM_015012.4 ENSP00000433126.1 Q5BJD5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461068
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726836
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.493A>G (p.M165V) alteration is located in exon 5 (coding exon 5) of the TMEM41B gene. This alteration results from a A to G substitution at nucleotide position 493, causing the methionine (M) at amino acid position 165 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.011
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
23
DANN
Benign
0.95
DEOGEN2
Benign
0.011
T;T;T
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.053
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.92
D;.;D
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.53
D;D;D
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.2
L;L;.
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-1.4
.;N;N
REVEL
Benign
0.19
Sift
Benign
0.033
.;D;D
Sift4G
Uncertain
0.033
D;D;T
Polyphen
0.018
B;B;.
Vest4
0.76
MutPred
0.45
Gain of catalytic residue at M165 (P = 0.0815);Gain of catalytic residue at M165 (P = 0.0815);Gain of catalytic residue at M165 (P = 0.0815);
MVP
0.56
MPC
0.28
ClinPred
0.87
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.19
gMVP
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1852868329; hg19: chr11-9309323; API