11-9295309-C-T

Variant names:

• chr11-9295309-C-T
• rs964366241
• NM_015012.4:c.318G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015012.4(TMEM41B):​c.318G>A​(p.Lys106Lys) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM41B NM_015012.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP7: Synonymous conserved (PhyloP=1.58 with no splicing effect.

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.318G>A	p.Lys106Lys	synonymous	Exon 3 of 7	NP_055827.1	Q5BJD5-1
	TMEM41B	NM_001165030.3		c.318G>A	p.Lys106Lys	synonymous	Exon 3 of 3	NP_001158502.1	Q5BJD5-3
	TMEM41B	NR_028491.3		n.470G>A		non_coding_transcript_exon	Exon 3 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM41B	ENST00000528080.6	TSL:1 MANE Select	c.318G>A	p.Lys106Lys	synonymous	Exon 3 of 7	ENSP00000433126.1	Q5BJD5-1
	TMEM41B	ENST00000611268.4	TSL:1	c.318G>A	p.Lys106Lys	synonymous	Exon 3 of 8	ENSP00000480141.1	Q5BJD5-1
	TMEM41B	ENST00000299596.8	TSL:1	n.318G>A		non_coding_transcript_exon	Exon 3 of 8	ENSP00000299596.4	Q5BJD5-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		1.6

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

Other links and lift over

dbSNP: rs964366241; hg19: chr11-9316856; COSMIC: COSV55154745;