19-35527009-C-T

Variant names:

• chr19-35527009-C-T
• rs745658693
• NM_001166034.2:c.1273G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001166034.2(SBSN):​c.1273G>A​(p.Asp425Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,545,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D425G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: SBSN NM_001166034.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.460
• Publications: 0 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.111772805).

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.1273G>A	p.Asp425Asn	missense	Exon 1 of 4	NP_001159506.1	Q6UWP8-1
	SBSN	NM_198538.4		c.376-132G>A		intron	N/A	NP_940940.1	Q6UWP8-2
	SBSN	NM_001166035.2		c.375+898G>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.1273G>A	p.Asp425Asn	missense	Exon 1 of 4	ENSP00000430242.1	Q6UWP8-1
	SBSN	ENST00000518157.1	TSL:1	c.376-132G>A		intron	N/A	ENSP00000428771.1	Q6UWP8-2
	SBSN	ENST00000588674.5	TSL:2	c.315+898G>A		intron	N/A	ENSP00000468646.2	K7ESC4

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 151986 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000479

GnomAD2 exomes AF: 0.0000526 AC: 8 AN: 151950 AF XY: 0.0000621

Gnomad AFR exome AF: 0.000351

Gnomad AMR exome AF: 0.000121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000330

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000201 AC: 28 AN: 1393018 Hom.: 0 Cov.: 42 AF XY: 0.0000204 AC XY: 14 AN XY: 687398

African (AFR) AF: 0.000443 AC: 14 AN: 31596

American (AMR) AF: 0.0000844 AC: 3 AN: 35534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25160

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35670

South Asian (SAS) AF: 0.00 AC: 0 AN: 79376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000742 AC: 8 AN: 1078518

Other (OTH) AF: 0.0000345 AC: 2 AN: 58022

GnomAD4 genome AF: 0.000118 AC: 18 AN: 151986 Hom.: 0 Cov.: 31 AF XY: 0.000135 AC XY: 10 AN XY: 74196

African (AFR) AF: 0.000387 AC: 16 AN: 41362

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000185

ExAC AF: 0.0000329 AC: 3

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	0.096
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.46
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.14
Sift	Benign	0.22	T
Sift4G	Benign	0.50	T
Vest4		0.14
MutPred		0.33		Gain of MoRF binding (P = 0.0555)
MVP		0.39
MPC		0.27
ClinPred		0.031	T
GERP RS		4.1
Varity_R		0.032
gMVP		0.0078
Mutation Taster		=93/7	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: rs745658693; hg19: chr19-36017911;