Variant 19-35526682-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001166034.2(SBSN):c.1600G>T(p.Val534Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000132 in 1,511,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 30)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

SBSN
NM_001166034.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3724346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBSN	NM_001166034.2 linkuse as main transcript	c.1600G>T	p.Val534Phe	missense_variant	1/4	ENST00000452271.7	NP_001159506.1	Q6UWP8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SBSN	ENST00000452271.7 linkuse as main transcript	c.1600G>T	p.Val534Phe	missense_variant	1/4	1	NM_001166034.2	ENSP00000430242.1	Q6UWP8-1
SBSN	ENST00000518157.1 linkuse as main transcript	c.571G>T	p.Val191Phe	missense_variant	2/5	1		ENSP00000428771.1	Q6UWP8-2
SBSN	ENST00000588674.5 linkuse as main transcript	c.315+1225G>T		intron_variant		2		ENSP00000468646.2	K7ESC4

Frequencies

GnomAD3 genomes

AF:

0.00000673

AC:

AN:

148528

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.34e-7

AC:

AN:

1362546

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

676922

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:

9.53e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000673

AC:

AN:

148528

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72272

show subpopulations

Gnomad4 AFR

AF:

0.0000246

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Oct 09, 2024

The c.1600G>T (p.V534F) alteration is located in exon 1 (coding exon 1) of the SBSN gene. This alteration results from a G to T substitution at nucleotide position 1600, causing the valine (V) at amino acid position 534 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Benign

-0.0089

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;.

Eigen

Benign

-0.025

Eigen_PC

Benign

-0.014

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.63

T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.37

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.061

Sift

Uncertain

0.0040

D;T

Sift4G

Benign

0.16

T;D

Vest4

0.53

MVP

0.60

MPC

1.1

ClinPred

0.94

GERP RS

2.9

Varity_R

0.18

gMVP

0.23

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