Variant chr19-35527213-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001166034.2(SBSN):c.1069G>A(p.Ala357Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,379,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SBSN
NM_001166034.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.482

Variant links:

Genes affected

SBSN (HGNC:24950): (suprabasin) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

SBSN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016616523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBSN	NM_001166034.2 linkuse as main transcript	c.1069G>A	p.Ala357Thr	missense_variant	1/4	ENST00000452271.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBSN	ENST00000452271.7 linkuse as main transcript	c.1069G>A	p.Ala357Thr	missense_variant	1/4	1	NM_001166034.2	P2	Q6UWP8-1
SBSN	ENST00000518157.1 linkuse as main transcript	c.376-336G>A		intron_variant		1		A2	Q6UWP8-2
SBSN	ENST00000588674.5 linkuse as main transcript	c.315+694G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149912

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000253

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000186

AC:

256

AN:

1379740

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

122

AN XY:

680444

show subpopulations

Gnomad4 AFR exome

AF:

0.0000320

Gnomad4 AMR exome

AF:

0.0000282

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000140

Gnomad4 SAS exome

AF:

0.0000508

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000221

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000133

AC:

AN:

150026

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

73204

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000133

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000213

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000253

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000385

Hom.:

ExAC

AF:

0.0000400

AC:

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

Jan 23, 2024

The c.1069G>A (p.A357T) alteration is located in exon 1 (coding exon 1) of the SBSN gene. This alteration results from a G to A substitution at nucleotide position 1069, causing the alanine (A) at amino acid position 357 to be replaced by a threonine (T). 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

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

4.2

DANN

Benign

0.62

DEOGEN2

Benign

0.0041

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.46

M_CAP

Benign

0.0095

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.3

REVEL

Benign

0.025

Sift

Benign

0.093

Sift4G

Uncertain

0.019

Vest4

0.081

MVP

0.16

MPC

0.26

ClinPred

0.018

GERP RS

2.0

Varity_R

0.028

gMVP

0.0051

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