Variant 11-9299691-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015012.4(TMEM41B):c.132G>C(p.Trp44Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TMEM41B
NM_015012.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0820

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]

TMEM41B 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=0.048492044).

BP6

Variant 11-9299691-C-G is Benign according to our data. Variant chr11-9299691-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3179472.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM41B	NM_015012.4 linkuse as main transcript	c.132G>C	p.Trp44Cys	missense_variant	2/7	ENST00000528080.6	NP_055827.1
TMEM41B	NM_001165030.3 linkuse as main transcript	c.132G>C	p.Trp44Cys	missense_variant	2/3		NP_001158502.1
TMEM41B	XM_047426969.1 linkuse as main transcript	c.132G>C	p.Trp44Cys	missense_variant	2/6		XP_047282925.1
TMEM41B	NR_028491.3 linkuse as main transcript	n.284G>C		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM41B	ENST00000528080.6 linkuse as main transcript	c.132G>C	p.Trp44Cys	missense_variant	2/7	1	NM_015012.4	ENSP00000433126	P1	Q5BJD5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243136

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000559

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

AF:

6.89e-7

AC:

AN:

1451424

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722064

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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.:

ExAC

AF:

0.00000824

AC:

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

Dec 12, 2023

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

0.096

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.00082

T;T;T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.64

T;.;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.048

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.4

N;N;.;N

MutationTaster

Benign

0.94

D;D;D

PrimateAI

Benign

0.27

PROVEAN

Benign

0.19

.;N;N;N

REVEL

Benign

0.086

Sift

Benign

0.21

.;T;T;T

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.21

MutPred

0.22

Loss of MoRF binding (P = 0.0867);Loss of MoRF binding (P = 0.0867);Loss of MoRF binding (P = 0.0867);Loss of MoRF binding (P = 0.0867);

MVP

0.10

MPC

0.36

ClinPred

0.11

GERP RS

-0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.091

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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