chr3-133369518-G-C

Variant names:

• chr3-133369518-G-C
• rs938229
• NM_023943.4:c.41-10234G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_023943.4(TMEM108):​c.41-10234G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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>C		intron	N/A	NP_076432.1
	LOC101927432	NR_189053.1		n.2095C>G		non_coding_transcript_exon	Exon 1 of 10
	TMEM108	NM_001136469.3		c.41-10234G>C		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>C		intron	N/A	ENSP00000324651.6
	TMEM108	ENST00000393130.7	TSL:1	c.41-10234G>C		intron	N/A	ENSP00000376838.3
	TMEM108	ENST00000515826.1	TSL:1	c.41-10234G>C		intron	N/A	ENSP00000423338.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 19602

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.52
DANN	Benign	0.38
PhyloP100		-0.14

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;