chr3-133297470-G-A

Variant names:

• chr3-133297470-G-A
• rs1708370
• NM_023943.4:c.40+68119G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023943.4(TMEM108):​c.40+68119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,110 control chromosomes in the GnomAD database, including 1,489 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 0.12 (1489 hom., cov: 33)
• Consequence: TMEM108 NM_023943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM108	NM_023943.4	c.40+68119G>A		intron_variant	Intron 3 of 5	ENST00000321871.11	NP_076432.1
TMEM108	NM_001136469.3	c.40+68119G>A		intron_variant	Intron 3 of 5		NP_001129941.1
TMEM108	NM_001282865.2	c.40+68119G>A		intron_variant	Intron 2 of 3		NP_001269794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM108	ENST00000321871.11	c.40+68119G>A		intron_variant	Intron 3 of 5	1	NM_023943.4	ENSP00000324651.6

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18027 AN: 151992 Hom.: 1490 Cov.: 33

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.119 AC: 18036 AN: 152110 Hom.: 1489 Cov.: 33 AF XY: 0.124 AC XY: 9236 AN XY: 74384

African (AFR) AF: 0.0568 AC: 2358 AN: 41486

American (AMR) AF: 0.214 AC: 3269 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0954 AC: 331 AN: 3470

East Asian (EAS) AF: 0.383 AC: 1976 AN: 5164

South Asian (SAS) AF: 0.173 AC: 836 AN: 4820

European-Finnish (FIN) AF: 0.153 AC: 1616 AN: 10586

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7194 AN: 67984

Other (OTH) AF: 0.132 AC: 279 AN: 2110

Alfa AF: 0.108 Hom.: 378

Bravo AF: 0.122

Asia WGS AF: 0.231 AC: 801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.47
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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: rs1708370; hg19: chr3-133016314;