rs746352021

Variant names:

• chr11-9299691-C-A
• NM_015012.4:c.132G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-9299691-C-A
• chr11-9299691-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015012.4(TMEM41B):​c.132G>T​(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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMEM41B NM_015012.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056350052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM41B	NM_015012.4	c.132G>T	p.Trp44Cys	missense_variant	Exon 2 of 7	ENST00000528080.6	NP_055827.1
TMEM41B	NM_001165030.3	c.132G>T	p.Trp44Cys	missense_variant	Exon 2 of 3		NP_001158502.1
TMEM41B	XM_047426969.1	c.132G>T	p.Trp44Cys	missense_variant	Exon 2 of 6		XP_047282925.1
TMEM41B	NR_028491.3	n.284G>T		non_coding_transcript_exon_variant	Exon 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM41B	ENST00000528080.6	c.132G>T	p.Trp44Cys	missense_variant	Exon 2 of 7	1	NM_015012.4	ENSP00000433126.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451424 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 722064

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.00082	T;T;T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.64	T;.;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.056	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.4	N;N;.;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.19	.;N;N;N
REVEL	Benign	0.16
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		0.40	T
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)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-9321238; COSMIC: COSV55154931;