Variant 13-52378187-G-A 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_018676.4(THSD1):c.1783C>T(p.Pro595Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

THSD1
NM_018676.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.867

Variant links:

Genes affected

THSD1 (HGNC:17754): (thrombospondin type 1 domain containing 1) The protein encoded by this gene contains a type 1 thrombospondin domain, which is found in a number of proteins involved in the complement pathway, as well as in extracellular matrix proteins. Alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Jan 2009]

THSD1 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=0.049357146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD1	NM_018676.4 linkuse as main transcript	c.1783C>T	p.Pro595Ser	missense_variant	5/5	ENST00000258613.5	NP_061146.1
THSD1	NM_199263.3 linkuse as main transcript	c.1624C>T	p.Pro542Ser	missense_variant	4/4		NP_954872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD1	ENST00000258613.5 linkuse as main transcript	c.1783C>T	p.Pro595Ser	missense_variant	5/5	1	NM_018676.4	ENSP00000258613	P1	Q9NS62-1
THSD1	ENST00000349258.8 linkuse as main transcript	c.1624C>T	p.Pro542Ser	missense_variant	4/4	1		ENSP00000340650		Q9NS62-2
THSD1	ENST00000648254.1 linkuse as main transcript	c.1624C>T	p.Pro542Ser	missense_variant	4/4			ENSP00000497520		Q9NS62-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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

Jun 23, 2021

The c.1783C>T (p.P595S) alteration is located in exon 5 (coding exon 4) of the THSD1 gene. This alteration results from a C to T substitution at nucleotide position 1783, causing the proline (P) at amino acid position 595 to be replaced by a serine (S). 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

0.086

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

8.8

DANN

Benign

0.78

DEOGEN2

Benign

0.014

.;T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.68

.;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.049

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.6

D;N;.

REVEL

Benign

0.042

Sift

Benign

0.23

T;T;.

Sift4G

Benign

0.38

T;T;.

Polyphen

0.012

B;B;B

Vest4

0.13

MutPred

0.13

.;Gain of phosphorylation at P595 (P = 0.0311);.;

MVP

0.12

MPC

0.26

ClinPred

0.071

GERP RS

1.9

Varity_R

0.024

gMVP

0.13

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