15-101652342-G-C

Variant names:

• chr15-101652342-G-C
• rs201667620
• NM_078474.3:c.20C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_078474.3(TM2D3):​c.20C>G​(p.Pro7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,447,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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: 36)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: TM2D3 NM_078474.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13122234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM2D3	NM_078474.3	c.20C>G	p.Pro7Arg	missense_variant	Exon 1 of 6	ENST00000333202.8	NP_510883.2
TM2D3	NM_025141.4	c.20C>G	p.Pro7Arg	missense_variant	Exon 1 of 5		NP_079417.2
TM2D3	NM_001308026.2	c.20C>G	p.Pro7Arg	missense_variant	Exon 1 of 6		NP_001294955.1
TM2D3	NM_001307960.2	c.20C>G	p.Pro7Arg	missense_variant	Exon 1 of 5		NP_001294889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM2D3	ENST00000333202.8	c.20C>G	p.Pro7Arg	missense_variant	Exon 1 of 6	1	NM_078474.3	ENSP00000330433.3

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1447838 Hom.: 0 Cov.: 43 AF XY: 0.00000278 AC XY: 2 AN XY: 720384

Gnomad4 AFR exome AF: 0.0000322

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000260

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 36

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.019
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	.;T;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.33	T;T;T;T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.55	.;.;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.61	N;N;N;N
REVEL	Benign	0.026
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Benign	0.084	T;T;T;T
Polyphen		0.0010	B;.;B;P
Vest4		0.14
MutPred		0.48		Gain of MoRF binding (P = 1e-04);Gain of MoRF binding (P = 1e-04);Gain of MoRF binding (P = 1e-04);Gain of MoRF binding (P = 1e-04);
MVP		0.040
MPC		0.082
ClinPred		0.11	T
GERP RS		-5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.063
gMVP		0.46

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: rs201667620; hg19: chr15-102192545;