rs1324276110

Variant names:

• chr1-155198113-C-A
• rs1324276110
• NM_007112.5:c.2182G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-155198113-C-A
• chr1-155198113-C-T

Variant summary

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

The NM_007112.5(THBS3):​c.2182G>T​(p.Ala728Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: THBS3 NM_007112.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.26
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007112.5. 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
	THBS3	NM_007112.5	MANE Select	c.2182G>T	p.Ala728Ser	missense	Exon 18 of 23	NP_009043.1	P49746-1
	THBS3	NM_001407490.1		c.2353G>T	p.Ala785Ser	missense	Exon 18 of 23	NP_001394419.1
	THBS3	NM_001407487.1		c.2191G>T	p.Ala731Ser	missense	Exon 18 of 23	NP_001394416.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS3	ENST00000368378.7	TSL:1 MANE Select	c.2182G>T	p.Ala728Ser	missense	Exon 18 of 23	ENSP00000357362.3	P49746-1
	THBS3	ENST00000541576.5	TSL:1	c.2155G>T	p.Ala719Ser	missense	Exon 17 of 22	ENSP00000444792.2	F5H4Z8
	THBS3	ENST00000541990.5	TSL:1	c.769G>T	p.Ala257Ser	missense	Exon 17 of 22	ENSP00000437353.1	Q2HIZ1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 33

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: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251396 AF XY: 0.0000368

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: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000233 AC: 34 AN: 1461856 Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1112010

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.059
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.00080	D
MutationAssessor	Benign	0.92	L
PhyloP100		3.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.39
Sift	Uncertain	0.018	D
Sift4G	Benign	0.55	T
Polyphen		0.061	B
Vest4		0.34
MutPred		0.50		Gain of sheet (P = 0.0101)
MVP		0.73
MPC		0.78
ClinPred		0.50	T
GERP RS		5.1
Varity_R		0.39
gMVP		0.45
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.47		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.47		Position offset: -9

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

Other links and lift over

dbSNP: rs1324276110; hg19: chr1-155167904;