3-133290970-G-A

Position:

• chr3-133290970-G-A

Variant summary

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

The NM_023943.4(TMEM108):​c.40+61619G>A variant causes a intron 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: 32)
• Consequence: TMEM108 NM_023943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

Genes affected

TMEM108 (HGNC:28451): (transmembrane protein 108) Predicted to be involved in several processes, including cellular response to brain-derived neurotrophic factor stimulus; nervous system development; and regulation of signal transduction. Predicted to be located in somatodendritic compartment. Predicted to be active in axon; endosome; and postsynaptic density. [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 (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM108	NM_023943.4	c.40+61619G>A		intron_variant		ENST00000321871.11	NP_076432.1
TMEM108	NM_001136469.3	c.40+61619G>A		intron_variant			NP_001129941.1
TMEM108	NM_001282865.2	c.40+61619G>A		intron_variant			NP_001269794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM108	ENST00000321871.11	c.40+61619G>A		intron_variant		1	NM_023943.4	ENSP00000324651	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.87

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

Other links and lift over

dbSNP: rs2370409; hg19: chr3-133009814;