15-101641980-A-G

Position:

• chr15-101641980-A-G

Variant summary

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

The NM_078474.3(TM2D3):​c.*499T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 985,380 control chromosomes in the GnomAD database, including 23,416 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 0.17 (2480 hom., cov: 33)
  • Exomes 𝑓: 0.22 (20936 hom.)
• Consequence: TM2D3 NM_078474.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TM2D3	NM_078474.3	c.*499T>C		3_prime_UTR_variant	6/6	ENST00000333202.8
TM2D3	NM_025141.4	c.*499T>C		3_prime_UTR_variant	5/5
TM2D3	NM_001307960.2	c.500+3107T>C		intron_variant
TM2D3	NM_001308026.2	c.578+3107T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TM2D3	ENST00000333202.8	c.*499T>C		3_prime_UTR_variant	6/6	1	NM_078474.3	A1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26085 AN: 152160 Hom.: 2475 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00845

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.221 AC: 184371 AN: 833104 Hom.: 20936 Cov.: 30 AF XY: 0.221 AC XY: 85164 AN XY: 384754

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.00358

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.171 AC: 26106 AN: 152276 Hom.: 2480 Cov.: 33 AF XY: 0.166 AC XY: 12366 AN XY: 74458

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.00828

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.167

Alfa AF: 0.188 Hom.: 2854

Bravo AF: 0.170

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.75
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

Publications

LitVar

Other links and lift over

dbSNP: rs708394; hg19: chr15-102182183;