19-35527209-G-C

Position:

• chr19-35527209-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001166034.2(SBSN):​c.1073C>G​(p.Ala358Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,384,048 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SBSN NM_001166034.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.51

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08179963).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBSN	NM_001166034.2	c.1073C>G	p.Ala358Gly	missense_variant	1/4	ENST00000452271.7	NP_001159506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBSN	ENST00000452271.7	c.1073C>G	p.Ala358Gly	missense_variant	1/4	1	NM_001166034.2	ENSP00000430242.1
SBSN	ENST00000518157.1	c.376-332C>G		intron_variant		1		ENSP00000428771.1
SBSN	ENST00000588674.5	c.315+698C>G		intron_variant		2		ENSP00000468646.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1384048 Hom.: 0 Cov.: 67 AF XY: 0.00 AC XY: 0 AN XY: 682942

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2024

The c.1073C>G (p.A358G) alteration is located in exon 1 (coding exon 1) of the SBSN gene. This alteration results from a C to G substitution at nucleotide position 1073, causing the alanine (A) at amino acid position 358 to be replaced by a glycine (G). 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	0.19
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.17
DANN	Benign	0.64
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.011
Sift	Benign	0.33	T
Sift4G	Benign	0.45	T
Vest4		0.16
MutPred		0.26		Loss of helix (P = 0.0376);
MVP		0.072
MPC		0.84
ClinPred		0.066	T
GERP RS		-1.5
Varity_R		0.043
gMVP		0.0024

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-36018111;