3-133369518-G-A

Variant names:

• chr3-133369518-G-A
• rs938229
• NM_023943.4:c.41-10234G>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.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
• Publications: 5 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]

LOC101927432 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023943.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM108	NM_023943.4	MANE Select	c.41-10234G>A		intron	N/A	NP_076432.1
	LOC101927432	NR_189053.1		n.2095C>T		non_coding_transcript_exon	Exon 1 of 10
	TMEM108	NM_001136469.3		c.41-10234G>A		intron	N/A	NP_001129941.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM108	ENST00000321871.11	TSL:1 MANE Select	c.41-10234G>A		intron	N/A	ENSP00000324651.6
	TMEM108	ENST00000393130.7	TSL:1	c.41-10234G>A		intron	N/A	ENSP00000376838.3
	TMEM108	ENST00000515826.1	TSL:1	c.41-10234G>A		intron	N/A	ENSP00000423338.1

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

African (AFR) AF: 0.291 AC: 12066 AN: 41414

American (AMR) AF: 0.417 AC: 6362 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3468

East Asian (EAS) AF: 0.417 AC: 2162 AN: 5180

South Asian (SAS) AF: 0.366 AC: 1757 AN: 4802

European-Finnish (FIN) AF: 0.428 AC: 4514 AN: 10546

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26588 AN: 67974

Other (OTH) AF: 0.405 AC: 858 AN: 2116

Alfa AF: 0.385 Hom.: 19602

Bravo AF: 0.368

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.30
PhyloP100		-0.14
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: rs938229; hg19: chr3-133088362;