11-9295280-G-A

Variant summary

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

The NM_015012.4(TMEM41B):​c.347C>T​(p.Ala116Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000035 in 1,571,900 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A116T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TMEM41B
NM_015012.4 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.95
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.347C>T p.Ala116Val missense_variant Exon 3 of 7 ENST00000528080.6 NP_055827.1 Q5BJD5-1
TMEM41BNM_001165030.3 linkc.347C>T p.Ala116Val missense_variant Exon 3 of 3 NP_001158502.1 Q5BJD5-3
TMEM41BXM_047426969.1 linkc.347C>T p.Ala116Val missense_variant Exon 3 of 6 XP_047282925.1
TMEM41BNR_028491.3 linkn.499C>T non_coding_transcript_exon_variant Exon 3 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM41BENST00000528080.6 linkc.347C>T p.Ala116Val missense_variant Exon 3 of 7 1 NM_015012.4 ENSP00000433126.1 Q5BJD5-1

Frequencies

GnomAD3 genomes
AF:
0.000223
AC:
34
AN:
152136
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000454
AC:
10
AN:
220394
Hom.:
0
AF XY:
0.0000420
AC XY:
5
AN XY:
119032
show subpopulations
Gnomad AFR exome
AF:
0.000634
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:
0.0000101
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000148
AC:
21
AN:
1419764
Hom.:
0
Cov.:
27
AF XY:
0.00000567
AC XY:
4
AN XY:
706050
show subpopulations
Gnomad4 AFR exome
AF:
0.000465
Gnomad4 AMR exome
AF:
0.0000506
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:
0.0000682
GnomAD4 genome
AF:
0.000223
AC:
34
AN:
152136
Hom.:
0
Cov.:
33
AF XY:
0.000242
AC XY:
18
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.000724
Gnomad4 AMR
AF:
0.000197
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000114
Hom.:
0
Bravo
AF:
0.000246
ESP6500AA
AF:
0.00114
AC:
5
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000579
AC:
7

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 24, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.347C>T (p.A116V) alteration is located in exon 3 (coding exon 3) of the TMEM41B gene. This alteration results from a C to T substitution at nucleotide position 347, causing the alanine (A) at amino acid position 116 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
Pathogenic
0.86
BayesDel_addAF
Benign
-0.033
T
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.095
T;T;T;.
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;.;D;D
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.45
T;T;T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Uncertain
2.1
M;M;.;M
PrimateAI
Pathogenic
0.91
D
PROVEAN
Uncertain
-2.7
.;D;D;D
REVEL
Uncertain
0.35
Sift
Uncertain
0.011
.;D;D;D
Sift4G
Benign
0.13
T;T;T;D
Polyphen
0.82
P;P;.;.
Vest4
0.78
MVP
0.63
MPC
0.58
ClinPred
0.28
T
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.43
gMVP
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: rs138570403; hg19: chr11-9316827; API