NM_003246.4:c.1802A>T

Variant names:

• chr15-39589230-A-T
• rs201454661
• NM_003246.4:c.1802A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003246.4(THBS1):​c.1802A>T​(p.Asn601Ile) 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 benign outcome for this variant. 16/22 in silico tools predict a benign 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. N601S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: THBS1 NM_003246.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• Publications: 3 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]

FSIP1 (HGNC:21674): (fibrous sheath interacting protein 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23770839).

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.1802A>T	p.Asn601Ile	missense	Exon 12 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.1802A>T	p.Asn601Ile	missense	Exon 12 of 22	ENSP00000260356.5	P07996-1
	THBS1	ENST00000880750.1		c.1802A>T	p.Asn601Ile	missense	Exon 13 of 23	ENSP00000550809.1
	THBS1	ENST00000880751.1		c.1802A>T	p.Asn601Ile	missense	Exon 13 of 23	ENSP00000550810.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251334 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.33	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.76	N
PhyloP100		1.6
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.27
Sift	Benign	0.26	T
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.30
MutPred		0.46		Loss of disorder (P = 0.0132)
MVP		0.62
MPC		0.54
ClinPred		0.17	T
GERP RS		4.5
Varity_R		0.12
gMVP		0.65

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

Other links and lift over

dbSNP: rs201454661; hg19: chr15-39881431;