chr1-155196000-C-G

Position:

• chr1-155196000-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007112.5(THBS3):​c.2799G>C​(p.Gln933His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: THBS3 NM_007112.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.819

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS3	NM_007112.5	c.2799G>C	p.Gln933His	missense_variant	22/23	ENST00000368378.7
THBS3-AS1	NR_183238.1	n.376+628C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS3	ENST00000368378.7	c.2799G>C	p.Gln933His	missense_variant	22/23	1	NM_007112.5	P3
THBS3-AS1	ENST00000685687.1	n.372+632C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2021

The c.2799G>C (p.Q933H) alteration is located in exon 22 (coding exon 22) of the THBS3 gene. This alteration results from a G to C substitution at nucleotide position 2799, causing the glutamine (Q) at amino acid position 933 to be replaced by a histidine (H). 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	0.18
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D;.;.;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Pathogenic	0.33	D
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Uncertain	0.27	D
MutationAssessor	Benign	0.69	N;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.8	N;.;N;N
REVEL	Uncertain	0.56
Sift	Uncertain	0.018	D;.;T;T
Sift4G	Uncertain	0.041	D;D;D;T
Polyphen		0.92	P;.;.;.
Vest4		0.41
MutPred		0.50		Loss of stability (P = 0.1811);.;.;.;
MVP		0.82
MPC		0.92
ClinPred		0.79	D
GERP RS		1.6
Varity_R		0.099
gMVP		0.42

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: chr1-155165791;