3-133290970-G-T

Position:

• chr3-133290970-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023943.4(TMEM108):​c.40+61619G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,020 control chromosomes in the GnomAD database, including 20,088 homozygotes. 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: 𝑓 0.49 (20088 hom., 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73930 AN: 151902 Hom.: 20081 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.486 AC: 73951 AN: 152020 Hom.: 20088 Cov.: 32 AF XY: 0.493 AC XY: 36627 AN XY: 74306

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.504

Alfa AF: 0.550 Hom.: 30726

Bravo AF: 0.483

Asia WGS AF: 0.652 AC: 2264 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.96
DANN	Benign	0.39

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;