19-35527170-C-T

Variant names:

• chr19-35527170-C-T
• rs2071385133
• NM_001166034.2:c.1112G>A

Variant summary

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

The NM_001166034.2(SBSN):​c.1112G>A​(p.Gly371Glu) 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: 33)
• Consequence: SBSN NM_001166034.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.959

Genes affected

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

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 rank	MANE	Protein	UniProt
SBSN	NM_001166034.2	c.1112G>A	p.Gly371Glu	missense_variant	Exon 1 of 4	ENST00000452271.7	NP_001159506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBSN	ENST00000452271.7	c.1112G>A	p.Gly371Glu	missense_variant	Exon 1 of 4	1	NM_001166034.2	ENSP00000430242.1
SBSN	ENST00000518157.1	c.376-293G>A		intron_variant	Intron 1 of 4	1		ENSP00000428771.1
SBSN	ENST00000588674.5	c.315+737G>A		intron_variant	Intron 1 of 3	2		ENSP00000468646.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1112G>A (p.G371E) 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 1112, causing the glycine (G) at amino acid position 371 to be replaced by a glutamic acid (E). 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	0.34
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.018
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.31
Sift	Benign	0.076	T
Sift4G	Benign	0.27	T
Vest4		0.79
MutPred		0.40		Gain of solvent accessibility (P = 0.0411);
MVP		0.64
MPC		1.1
ClinPred		0.97	D
GERP RS		4.6
Varity_R		0.27
gMVP		0.039

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

Other links and lift over

dbSNP: rs2071385133; hg19: chr19-36018072;