rs201608649

Variant names:

• chr1-155197134-C-A
• NM_007112.5:c.2579G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-155197134-C-A
• chr1-155197134-C-G
• chr1-155197134-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_007112.5(THBS3):​c.2579G>T​(p.Arg860Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R860Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: THBS3 NM_007112.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379

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

ACMG classification

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, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS3	NM_007112.5	c.2579G>T	p.Arg860Leu	missense_variant	Exon 21 of 23	ENST00000368378.7	NP_009043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS3	ENST00000368378.7	c.2579G>T	p.Arg860Leu	missense_variant	Exon 21 of 23	1	NM_007112.5	ENSP00000357362.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.90	D;.;.;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.36	N
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.80	D;D;D;D
MetaSVM	Uncertain	0.041	D
MutationAssessor	Benign	2.0	M;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.7	D;.;D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0010	D;.;D;D
Sift4G	Uncertain	0.029	D;D;D;T
Polyphen		1.0	D;.;.;.
Vest4		0.63
MutPred		0.79		Loss of MoRF binding (P = 0.0064);.;.;.;
MVP		0.67
MPC		1.0
ClinPred		0.98	D
GERP RS		3.6
Varity_R		0.58
gMVP		0.59

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.

Other links and lift over

hg19: chr1-155166925;