Variant 11-9295319-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015012.4(TMEM41B):c.308C>T(p.Ser103Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,446,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

TMEM41B
NM_015012.4 missense

Scores

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]

TMEM41B links:

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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/exons	MANE	Protein
TMEM41B	NM_015012.4 linkuse as main transcript	c.308C>T	p.Ser103Phe	missense_variant	3/7	ENST00000528080.6	NP_055827.1
TMEM41B	NM_001165030.3 linkuse as main transcript	c.308C>T	p.Ser103Phe	missense_variant	3/3		NP_001158502.1
TMEM41B	XM_047426969.1 linkuse as main transcript	c.308C>T	p.Ser103Phe	missense_variant	3/6		XP_047282925.1
TMEM41B	NR_028491.3 linkuse as main transcript	n.460C>T		non_coding_transcript_exon_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM41B	ENST00000528080.6 linkuse as main transcript	c.308C>T	p.Ser103Phe	missense_variant	3/7	1	NM_015012.4	ENSP00000433126	P1	Q5BJD5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000419

AC:

AN:

238890

Hom.:

AF XY:

0.00000774

AC XY:

AN XY:

129118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000344

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1446858

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

719518

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:

0.0000473

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.308C>T (p.S103F) 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 308, causing the serine (S) at amino acid position 103 to be replaced by a phenylalanine (F). 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

0.73

BayesDel_addAF

Pathogenic

0.46

BayesDel_noAF

Pathogenic

0.42

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;T;.

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;.;D;D

M_CAP

Benign

0.0067

MetaRNN

Uncertain

0.71

D;D;D;D

MetaSVM

Uncertain

0.096

MutationAssessor

Uncertain

2.4

M;M;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-4.5

.;D;D;D

REVEL

Uncertain

0.61

Sift

Uncertain

0.0050

.;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.90

MutPred

0.40

Loss of disorder (P = 0.0319);Loss of disorder (P = 0.0319);Loss of disorder (P = 0.0319);Loss of disorder (P = 0.0319);

MVP

0.40

MPC

0.85

ClinPred

0.97

GERP RS

5.3

Varity_R

0.63

gMVP

0.85

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

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