Genetic Variant TMEM41B:p.Glu82Asp (chr11-9295381-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015012.4(TMEM41B):c.246A>C(p.Glu82Asp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMEM41B
NM_015012.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3054567).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015012.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM41B	NM_015012.4	MANE Select	c.246A>C	p.Glu82Asp	missense	Exon 3 of 7	NP_055827.1	Q5BJD5-1
TMEM41B	NM_001165030.3		c.246A>C	p.Glu82Asp	missense	Exon 3 of 3	NP_001158502.1	Q5BJD5-3
TMEM41B	NR_028491.3		n.398A>C		non_coding_transcript_exon	Exon 3 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM41B	ENST00000528080.6	TSL:1 MANE Select	c.246A>C	p.Glu82Asp	missense	Exon 3 of 7	ENSP00000433126.1	Q5BJD5-1
TMEM41B	ENST00000611268.4	TSL:1	c.246A>C	p.Glu82Asp	missense	Exon 3 of 8	ENSP00000480141.1	Q5BJD5-1
TMEM41B	ENST00000299596.8	TSL:1	n.246A>C		non_coding_transcript_exon	Exon 3 of 8	ENSP00000299596.4	Q5BJD5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1422342

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707620

African (AFR)

AF:

0.00

AC:

AN:

31586

American (AMR)

AF:

0.00

AC:

AN:

35786

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24744

East Asian (EAS)

AF:

0.00

AC:

AN:

39020

South Asian (SAS)

AF:

0.00

AC:

AN:

79762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52838

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5452

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094220

Other (OTH)

AF:

0.00

AC:

AN:

58934

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Benign

-0.10

Eigen_PC

Benign

0.033

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.027

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.1

PhyloP100

2.5

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.9

REVEL

Benign

0.19

Sift

Benign

0.13

Sift4G

Benign

0.22

Polyphen

0.23

Vest4

0.69

MutPred

0.27

Gain of ubiquitination at K87 (P = 0.1106)

MVP

0.37

MPC

0.27

ClinPred

0.59

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.85

Mutation Taster

=13/87

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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