Variant 8-73067421-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153225.4(SBSPON):c.715C>T(p.Arg239Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,428 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000089 ( 1 hom. )

Consequence

SBSPON
NM_153225.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15

Variant links:

Genes affected

SBSPON (HGNC:30362): (somatomedin B and thrombospondin type 1 domain containing) Predicted to be an extracellular matrix structural constituent. Colocalizes with collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

SBSPON links:

SBSPON (HGNC:):

SBSPON links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24062338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBSPON	NM_153225.4 linkuse as main transcript	c.715C>T	p.Arg239Trp	missense_variant	5/5	ENST00000297354.7	NP_694957.3	Q8IVN8
SBSPON	XM_047421408.1 linkuse as main transcript	c.613C>T	p.Arg205Trp	missense_variant	6/6		XP_047277364.1
SBSPON	XM_017013145.2 linkuse as main transcript	c.529C>T	p.Arg177Trp	missense_variant	5/5		XP_016868634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBSPON	ENST00000297354.7 linkuse as main transcript	c.715C>T	p.Arg239Trp	missense_variant	5/5	1	NM_153225.4	ENSP00000297354.6		Q8IVN8
SBSPON	ENST00000519697.1 linkuse as main transcript	n.1083C>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1459428

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726206

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 26, 2023

The c.715C>T (p.R239W) alteration is located in exon 5 (coding exon 5) of the SBSPON gene. This alteration results from a C to T substitution at nucleotide position 715, causing the arginine (R) at amino acid position 239 to be replaced by a tryptophan (W). 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

0.11

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0092

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.012

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.19

Sift

Benign

0.078

Sift4G

Benign

0.16

Polyphen

1.0

Vest4

0.19

MutPred

0.35

Gain of MoRF binding (P = 0.1334);

MVP

0.58

MPC

0.77

ClinPred

0.96

GERP RS

4.2

Varity_R

0.10

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over