3-133381608-G-A

Variant names:

• chr3-133381608-G-A
• rs1197313
• NM_023943.4:c.1450+447G>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.1450+447G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,002 control chromosomes in the GnomAD database, including 11,301 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 0.38 (11301 hom., cov: 31)
• Consequence: TMEM108 NM_023943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 3 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]

ENSG00000300103 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM108	NM_023943.4	c.1450+447G>A		intron_variant	Intron 4 of 5	ENST00000321871.11	NP_076432.1
TMEM108	NM_001136469.3	c.1450+447G>A		intron_variant	Intron 4 of 5		NP_001129941.1
TMEM108	NM_001282865.2	c.41-8572G>A		intron_variant	Intron 2 of 3		NP_001269794.1
LOC101927432	NR_189054.1	n.131+55C>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM108	ENST00000321871.11	c.1450+447G>A		intron_variant	Intron 4 of 5	1	NM_023943.4	ENSP00000324651.6

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57387 AN: 151884 Hom.: 11299 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.378 AC: 57416 AN: 152002 Hom.: 11301 Cov.: 31 AF XY: 0.380 AC XY: 28228 AN XY: 74306

African (AFR) AF: 0.256 AC: 10607 AN: 41484

American (AMR) AF: 0.412 AC: 6290 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1583 AN: 3470

East Asian (EAS) AF: 0.422 AC: 2180 AN: 5164

South Asian (SAS) AF: 0.403 AC: 1935 AN: 4804

European-Finnish (FIN) AF: 0.445 AC: 4703 AN: 10570

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28818 AN: 67934

Other (OTH) AF: 0.399 AC: 840 AN: 2106

Alfa AF: 0.410 Hom.: 22034

Bravo AF: 0.369

Asia WGS AF: 0.358 AC: 1248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0030
DANN	Benign	0.60
PhyloP100		-1.6
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: rs1197313; hg19: chr3-133100452;