NM_015012.4:c.718C>T

Variant names:

• chr11-9283582-G-A
• rs1343354056
• NM_015012.4:c.718C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015012.4(TMEM41B):​c.718C>T​(p.Pro240Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM41B NM_015012.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.756

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM41B	NM_015012.4	MANE Select	c.718C>T	p.Pro240Ser	missense	Exon 7 of 7	NP_055827.1	Q5BJD5-1
	TMEM41B	NR_028491.3		n.870C>T		non_coding_transcript_exon	Exon 7 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM41B	ENST00000528080.6	TSL:1 MANE Select	c.718C>T	p.Pro240Ser	missense	Exon 7 of 7	ENSP00000433126.1	Q5BJD5-1
	TMEM41B	ENST00000611268.4	TSL:1	c.718C>T	p.Pro240Ser	missense	Exon 7 of 8	ENSP00000480141.1	Q5BJD5-1
	TMEM41B	ENST00000299596.8	TSL:1	n.718C>T		non_coding_transcript_exon	Exon 7 of 8	ENSP00000299596.4	Q5BJD5-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.097	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		10
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.73
MutPred		0.58		Loss of catalytic residue at P239 (P = 0.0137)
MVP		0.80
MPC		0.85
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.59
gMVP		0.90
Mutation Taster		=5/95	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1343354056; hg19: chr11-9305129; COSMIC: COSV55154370; COSMIC: COSV55154370;