NM_003246.4:c.75C>G

Variant names:

• chr15-39582200-C-G
• rs59086883
• NM_003246.4:c.75C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003246.4(THBS1):​c.75C>G​(p.Gly25Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G25G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: THBS1 NM_003246.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.505
• Publications: 1 publications found

Genes affected

THBS1 (HGNC:11785): (thrombospondin 1) The protein encoded by this gene is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1. This protein has been shown to play roles in platelet aggregation, angiogenesis, and tumorigenesis. [provided by RefSeq, Jul 2008]

THBS1 Gene-Disease associations (from GenCC):

• congenital glaucoma

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=0.505 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003246.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS1	NM_003246.4	MANE Select	c.75C>G	p.Gly25Gly	synonymous	Exon 3 of 22	NP_003237.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS1	ENST00000260356.6	TSL:1 MANE Select	c.75C>G	p.Gly25Gly	synonymous	Exon 3 of 22	ENSP00000260356.5	P07996-1
	THBS1	ENST00000880750.1		c.75C>G	p.Gly25Gly	synonymous	Exon 4 of 23	ENSP00000550809.1
	THBS1	ENST00000880751.1		c.75C>G	p.Gly25Gly	synonymous	Exon 4 of 23	ENSP00000550810.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000380 AC: 9 AN: 237140 AF XY: 0.0000312

Gnomad AFR exome AF: 0.000568

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.5
DANN	Benign	0.73
PhyloP100		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs59086883; hg19: chr15-39874401;