rs938229

Positions:

• chr3-133369518-G-A
• chr3-133369518-G-C

Variant summary

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

The NM_023943.4(TMEM108):​c.41-10234G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,976 control chromosomes in the GnomAD database, including 10,732 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 0.37 (10732 hom., cov: 32)
• Consequence: TMEM108 NM_023943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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]

LOC101927432 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM108	NM_023943.4	c.41-10234G>A		intron_variant		ENST00000321871.11
LOC101927432	XR_007096099.1	n.5958-965C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM108	ENST00000321871.11	c.41-10234G>A		intron_variant		1	NM_023943.4	P1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56257 AN: 151858 Hom.: 10719 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.370 AC: 56303 AN: 151976 Hom.: 10732 Cov.: 32 AF XY: 0.371 AC XY: 27587 AN XY: 74268

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.405

Alfa AF: 0.386 Hom.: 15599

Bravo AF: 0.368

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.30

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: rs938229; hg19: chr3-133088362;