Variant chr8-73067366-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153225.4(SBSPON):c.770C>T(p.Ala257Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000225 in 1,599,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

SBSPON
NM_153225.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06743601).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBSPON	NM_153225.4 linkuse as main transcript	c.770C>T	p.Ala257Val	missense_variant	5/5	ENST00000297354.7	NP_694957.3	Q8IVN8
SBSPON	XM_047421408.1 linkuse as main transcript	c.668C>T	p.Ala223Val	missense_variant	6/6		XP_047277364.1
SBSPON	XM_017013145.2 linkuse as main transcript	c.584C>T	p.Ala195Val	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.770C>T	p.Ala257Val	missense_variant	5/5	1	NM_153225.4	ENSP00000297354.6		Q8IVN8
SBSPON	ENST00000519697.1 linkuse as main transcript	n.1138C>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151644

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000221

AC:

AN:

1448202

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

721436

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000264

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151644

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74040

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000227

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 28, 2022

The c.770C>T (p.A257V) 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 770, causing the alanine (A) at amino acid position 257 to be replaced by a valine (V). 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

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0022

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.019

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.72

M_CAP

Benign

0.0041

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.61

REVEL

Benign

0.044

Sift

Benign

0.28

Sift4G

Benign

0.32

Polyphen

0.078

Vest4

0.071

MutPred

0.34

Loss of loop (P = 0.1242);

MVP

0.13

MPC

0.24

ClinPred

0.28

GERP RS

4.1

Varity_R

0.069

gMVP

0.29

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

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