rs708394

Variant names:

• chr15-101641980-A-C
• rs708394
• ENST00000559891.1:n.2001T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-101641980-A-C
• chr15-101641980-A-G

Variant summary

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

The ENST00000559891.1(TM2D3):​n.2001T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000012 in 833,274 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: TM2D3 ENST00000559891.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 14 publications found

Genes affected

TM2D3 (HGNC:24128): (TM2 domain containing 3) The protein encoded by this gene contains a structural module related to that of the seven transmembrane domain G protein-coupled receptor superfamily. This protein has sequence and structural similarities to the beta-amyloid binding protein (BBP), but, unlike BBP, it does not regulate a response to beta-amyloid peptide. This protein may have regulatory roles in cell death or proliferation signal cascades. Several alternatively spliced transcript variants of this gene are described but the full length nature of some variants has not been determined. Multiple polyadenylation sites have been found in this gene. [provided by RefSeq, Jul 2008]

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=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM2D3	NM_078474.3	c.*499T>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000333202.8	NP_510883.2
TM2D3	NM_025141.4	c.*499T>G		3_prime_UTR_variant	Exon 5 of 5		NP_079417.2
TM2D3	NM_001308026.2	c.578+3107T>G		intron_variant	Intron 5 of 5		NP_001294955.1
TM2D3	NM_001307960.2	c.500+3107T>G		intron_variant	Intron 4 of 4		NP_001294889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM2D3	ENST00000333202.8	c.*499T>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_078474.3	ENSP00000330433.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 833274 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 384834

African (AFR) AF: 0.00 AC: 0 AN: 15786

American (AMR) AF: 0.00 AC: 0 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5152

East Asian (EAS) AF: 0.00 AC: 0 AN: 3630

South Asian (SAS) AF: 0.00 AC: 0 AN: 16570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1620

European-Non Finnish (NFE) AF: 0.00000131 AC: 1 AN: 761954

Other (OTH) AF: 0.00 AC: 0 AN: 27298

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 3662

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.89
DANN	Benign	0.73
PhyloP100		-0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs708394; hg19: chr15-102182183;