chr3-133081302-C-A

Variant names:

• chr3-133081302-C-A
• rs10935045
• NM_023943.4:c.-47+35282C>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.-47+35282C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,150 control chromosomes in the GnomAD database, including 1,642 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 0.15 (1642 hom., cov: 32)
• Consequence: TMEM108 NM_023943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 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.-47+35282C>A		intron	N/A	NP_076432.1
	TMEM108	NM_001136469.3		c.-43+35282C>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.-47+35282C>A		intron	N/A	ENSP00000324651.6
	TMEM108	ENST00000393130.7	TSL:1	c.-43+35282C>A		intron	N/A	ENSP00000376838.3
	TMEM108	ENST00000512137.5	TSL:3	c.-47+35282C>A		intron	N/A	ENSP00000426301.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22379 AN: 152032 Hom.: 1635 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.147 AC: 22404 AN: 152150 Hom.: 1642 Cov.: 32 AF XY: 0.148 AC XY: 11004 AN XY: 74390

African (AFR) AF: 0.147 AC: 6109 AN: 41504

American (AMR) AF: 0.168 AC: 2573 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 277 AN: 3472

East Asian (EAS) AF: 0.185 AC: 954 AN: 5166

South Asian (SAS) AF: 0.156 AC: 750 AN: 4816

European-Finnish (FIN) AF: 0.182 AC: 1925 AN: 10584

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9417 AN: 68006

Other (OTH) AF: 0.143 AC: 301 AN: 2112

Alfa AF: 0.118 Hom.: 600

Bravo AF: 0.146

Asia WGS AF: 0.154 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.69
PhyloP100		-0.28
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: rs10935045; hg19: chr3-132800146;