Variant chr1-155197555-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_007112.5(THBS3):c.2407C>A(p.Arg803Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

THBS3
NM_007112.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23

Variant links:

Genes affected

THBS3 (HGNC:11787): (thrombospondin 3) The protein encoded by this gene belongs to the thrombospondin family. Thrombospondin family members are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. This protein forms a pentameric molecule linked by a single disulfide bond. This gene shares a common promoter with metaxin 1. Alternate splicing results in coding and non-coding transcript variants. [provided by RefSeq, Nov 2011]

THBS3 links:

THBS3-AS1 (HGNC:40582): (THBS3 antisense RNA 1)

THBS3-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2883063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS3	NM_007112.5 linkuse as main transcript	c.2407C>A	p.Arg803Ser	missense_variant	20/23	ENST00000368378.7
THBS3-AS1	NR_183238.1 linkuse as main transcript	n.543+538G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS3	ENST00000368378.7 linkuse as main transcript	c.2407C>A	p.Arg803Ser	missense_variant	20/23	1	NM_007112.5	P3	P49746-1
THBS3-AS1	ENST00000685687.1 linkuse as main transcript	n.539+538G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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

Jul 25, 2023

The c.2407C>A (p.R803S) alteration is located in exon 20 (coding exon 20) of the THBS3 gene. This alteration results from a C to A substitution at nucleotide position 2407, causing the arginine (R) at amino acid position 803 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

0.20

BayesDel_addAF

Uncertain

0.077

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.41

T;.;.;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Benign

-0.67

N;.;.;.

MutationTaster

Benign

0.52

D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

2.7

N;.;N;N

REVEL

Uncertain

0.39

Sift

Benign

1.0

T;.;T;T

Sift4G

Benign

0.61

T;T;T;T

Polyphen

0.099

B;.;.;.

Vest4

0.35

MutPred

0.75

Loss of MoRF binding (P = 0.0683);.;.;.;

MVP

0.69

MPC

0.40

ClinPred

0.85

GERP RS

4.8

Varity_R

0.084

gMVP

0.34

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