chr19-35527213-C-T

Variant names:

• chr19-35527213-C-T
• rs546545575
• NM_001166034.2:c.1069G>A

Variant summary

Our verdict is Likely benign. The variant received -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. 17/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.482
• Publications: 6 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016616523).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166034.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBSN	NM_001166034.2	MANE Select	c.1069G>A	p.Ala357Thr	missense	Exon 1 of 4	NP_001159506.1	Q6UWP8-1
	SBSN	NM_198538.4		c.376-336G>A		intron	N/A	NP_940940.1	Q6UWP8-2
	SBSN	NM_001166035.2		c.375+694G>A		intron	N/A	NP_001159507.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBSN	ENST00000452271.7	TSL:1 MANE Select	c.1069G>A	p.Ala357Thr	missense	Exon 1 of 4	ENSP00000430242.1	Q6UWP8-1
	SBSN	ENST00000518157.1	TSL:1	c.376-336G>A		intron	N/A	ENSP00000428771.1	Q6UWP8-2
	SBSN	ENST00000588674.5	TSL:2	c.315+694G>A		intron	N/A	ENSP00000468646.2	K7ESC4

Frequencies

GnomAD3 genomes AF: 0.000133 AC: 20 AN: 149912 Hom.: 0 Cov.: 34

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

GnomAD2 exomes AF: 0.000120 AC: 17 AN: 141340 AF XY: 0.0000794

Gnomad AFR exome AF: 0.000132

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000259

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000186 AC: 256 AN: 1379740 Hom.: 0 Cov.: 58 AF XY: 0.000179 AC XY: 122 AN XY: 680444

African (AFR) AF: 0.0000320 AC: 1 AN: 31274

American (AMR) AF: 0.0000282 AC: 1 AN: 35446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25080

East Asian (EAS) AF: 0.000140 AC: 5 AN: 35670

South Asian (SAS) AF: 0.0000508 AC: 4 AN: 78778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34916

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5672

European-Non Finnish (NFE) AF: 0.000221 AC: 238 AN: 1075264

Other (OTH) AF: 0.000104 AC: 6 AN: 57640

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000133 AC: 20 AN: 150026 Hom.: 0 Cov.: 34 AF XY: 0.000123 AC XY: 9 AN XY: 73204

African (AFR) AF: 0.00 AC: 0 AN: 40894

American (AMR) AF: 0.000133 AC: 2 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.000213 AC: 1 AN: 4688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000253 AC: 17 AN: 67186

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.000271 Hom.: 0

ExAC AF: 0.0000400 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.2
DANN	Benign	0.62
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.48
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.025
Sift	Benign	0.093	T
Sift4G	Uncertain	0.019	D
Vest4		0.081
MVP		0.16
MPC		0.26
ClinPred		0.018	T
GERP RS		2.0
Varity_R		0.028
gMVP		0.0051
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs546545575; hg19: chr19-36018115;