chr19-35527218-T-G

Position:

• chr19-35527218-T-G

Variant summary

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

The NM_001166034.2(SBSN):​c.1064A>C​(p.His355Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: SBSN NM_001166034.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.663

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/exons	MANE	UniProt
SBSN	NM_001166034.2	c.1064A>C	p.His355Pro	missense_variant	1/4	ENST00000452271.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBSN	ENST00000452271.7	c.1064A>C	p.His355Pro	missense_variant	1/4	1	NM_001166034.2	P2
SBSN	ENST00000518157.1	c.376-341A>C		intron_variant		1		A2
SBSN	ENST00000588674.5	c.315+689A>C		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 66

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

Apr 06, 2023

The c.1064A>C (p.H355P) alteration is located in exon 1 (coding exon 1) of the SBSN gene. This alteration results from a A to C substitution at nucleotide position 1064, causing the histidine (H) at amino acid position 355 to be replaced by a proline (P). 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	0.27
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.15
Sift	Benign	0.21	T
Sift4G	Benign	0.076	T
Vest4		0.58
MutPred		0.33		Gain of relative solvent accessibility (P = 0.0479);
MVP		0.45
MPC		1.1
ClinPred		0.67	D
GERP RS		4.2
Varity_R		0.30
gMVP		0.041

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: chr19-36018120;