Variant 15-71215110-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024817.3(THSD4):c.175T>G(p.Trp59Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

THSD4
NM_024817.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70

Variant links:

Genes affected

THSD4 (HGNC:25835): (thrombospondin type 1 domain containing 4) Predicted to enable hydrolase activity. Predicted to be an extracellular matrix structural constituent. Predicted to act upstream of or within elastic fiber assembly. Located in collagen-containing extracellular matrix and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

THSD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.792

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
THSD4	NM_024817.3 linkuse as main transcript	c.175T>G	p.Trp59Gly	missense_variant	4/18	ENST00000261862.8
THSD4	NM_001394532.1 linkuse as main transcript	c.175T>G	p.Trp59Gly	missense_variant	4/18
THSD4	XM_047433080.1 linkuse as main transcript	c.175T>G	p.Trp59Gly	missense_variant	4/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8 linkuse as main transcript	c.175T>G	p.Trp59Gly	missense_variant	4/18	5	NM_024817.3	P1	Q6ZMP0-1
THSD4	ENST00000355327.7 linkuse as main transcript	c.175T>G	p.Trp59Gly	missense_variant	4/18	5		P1	Q6ZMP0-1
THSD4	ENST00000620694.1 linkuse as main transcript	c.175T>G	p.Trp59Gly	missense_variant	4/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1189876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

579934

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.175T>G (p.W59G) alteration is located in exon 3 (coding exon 3) of the THSD4 gene. This alteration results from a T to G substitution at nucleotide position 175, causing the tryptophan (W) at amino acid position 59 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.25

T;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.72

T;T

M_CAP

Pathogenic

0.56

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Uncertain

-0.066

MutationAssessor

Pathogenic

3.7

H;.

MutationTaster

Benign

0.96

D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-5.0

D;.

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.94

P;.

Vest4

0.75

MutPred

0.57

Loss of MoRF binding (P = 0.0426);Loss of MoRF binding (P = 0.0426);

MVP

0.53

MPC

0.75

ClinPred

0.99

GERP RS

4.3

Varity_R

0.77

gMVP

0.81

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over