Variant rs374360447 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_078474.3(TM2D3):c.38C>T(p.Ala13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,026 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: 35)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TM2D3
NM_078474.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.362

Variant links:

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]

TM2D3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058584213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM2D3	NM_078474.3 link	c.38C>T	p.Ala13Val	missense_variant	Exon 1 of 6	ENST00000333202.8	NP_510883.2	Q9BRN9-1
TM2D3	NM_025141.4 link	c.38C>T	p.Ala13Val	missense_variant	Exon 1 of 5		NP_079417.2	Q9BRN9-2
TM2D3	NM_001308026.2 link	c.38C>T	p.Ala13Val	missense_variant	Exon 1 of 6		NP_001294955.1	H0YNS4B4DLL2
TM2D3	NM_001307960.2 link	c.38C>T	p.Ala13Val	missense_variant	Exon 1 of 5		NP_001294889.1	E7EPS7B4DLL2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM2D3	ENST00000333202.8 link	c.38C>T	p.Ala13Val	missense_variant	Exon 1 of 6	1	NM_078474.3	ENSP00000330433.3		Q9BRN9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450026

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721532

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

2.1

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0076

.;T;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.41

T;T;T;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.059

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;.;N;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.15

N;N;N;N

REVEL

Benign

0.0070

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.0060

B;.;B;B

Vest4

0.19

MutPred

0.27

Loss of helix (P = 0.0304);Loss of helix (P = 0.0304);Loss of helix (P = 0.0304);Loss of helix (P = 0.0304);

MVP

0.030

MPC

0.070

ClinPred

0.11

GERP RS

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.037

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over