Variant 15-71215363-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024817.3(THSD4):c.428C>T(p.Pro143Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000326 in 1,532,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

THSD4
NM_024817.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

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:

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ACMG classification

Classification made for transcript

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=0.076147735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD4	NM_024817.3 linkuse as main transcript	c.428C>T	p.Pro143Leu	missense_variant	4/18	ENST00000261862.8	NP_079093.2	Q6ZMP0-1
THSD4	NM_001394532.1 linkuse as main transcript	c.428C>T	p.Pro143Leu	missense_variant	4/18		NP_001381461.1
THSD4	XM_047433080.1 linkuse as main transcript	c.428C>T	p.Pro143Leu	missense_variant	4/18		XP_047289036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8 linkuse as main transcript	c.428C>T	p.Pro143Leu	missense_variant	4/18	5	NM_024817.3	ENSP00000261862.8		Q6ZMP0-1
THSD4	ENST00000355327.7 linkuse as main transcript	c.428C>T	p.Pro143Leu	missense_variant	4/18	5		ENSP00000347484.3		Q6ZMP0-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1380088

Hom.:

Cov.:

AF XY:

0.00000294

AC XY:

AN XY:

680942

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000562

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

AF:

0.0000197

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Nov 13, 2023

The c.428C>T (p.P143L) alteration is located in exon 3 (coding exon 3) of the THSD4 gene. This alteration results from a C to T substitution at nucleotide position 428, causing the proline (P) at amino acid position 143 to be replaced by a leucine (L). 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

Benign

0.079

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.033

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.70

M_CAP

Benign

0.042

MetaRNN

Benign

0.076

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.1

REVEL

Benign

0.090

Sift

Benign

0.19

Sift4G

Benign

0.26

Polyphen

0.0010

Vest4

0.17

MutPred

0.52

Gain of MoRF binding (P = 0.0346);

MVP

0.21

MPC

0.12

ClinPred

0.17

GERP RS

3.7

Varity_R

0.082

gMVP

0.39

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over