rs17256082

Variant names:

• chr2-174427636-T-C
• rs17256082
• NM_024583.5:c.1093-77T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000272732.11(SCRN3):​c.1093-77T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 798,368 control chromosomes in the GnomAD database, including 38,943 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6096 hom., cov: 32)
  • Exomes 𝑓: 0.31 (32847 hom.)
• Consequence: SCRN3 ENST00000272732.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• Publications: 13 publications found

Genes affected

SCRN3 (HGNC:30382): (secernin 3) Predicted to enable cysteine-type exopeptidase activity and dipeptidase activity. Predicted to be involved in proteolysis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000272732.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCRN3	NM_024583.5	MANE Select	c.1093-77T>C		intron	N/A	NP_078859.2
	SCRN3	NM_001412210.1		c.1153-77T>C		intron	N/A	NP_001399139.1
	SCRN3	NM_001412202.1		c.1093-77T>C		intron	N/A	NP_001399131.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCRN3	ENST00000272732.11	TSL:1 MANE Select	c.1093-77T>C		intron	N/A	ENSP00000272732.6
	SCRN3	ENST00000548921.5	TSL:1	n.528-77T>C		intron	N/A
	SCRN3	ENST00000409673.7	TSL:2	c.1072-77T>C		intron	N/A	ENSP00000387142.3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40316 AN: 151932 Hom.: 6098 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.313 AC: 202021 AN: 646318 Hom.: 32847 AF XY: 0.313 AC XY: 101407 AN XY: 323746

African (AFR) AF: 0.126 AC: 1865 AN: 14856

American (AMR) AF: 0.223 AC: 2913 AN: 13052

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 5885 AN: 13400

East Asian (EAS) AF: 0.242 AC: 6702 AN: 27674

South Asian (SAS) AF: 0.232 AC: 5979 AN: 25772

European-Finnish (FIN) AF: 0.303 AC: 11942 AN: 39350

Middle Eastern (MID) AF: 0.458 AC: 1039 AN: 2270

European-Non Finnish (NFE) AF: 0.326 AC: 156339 AN: 479944

Other (OTH) AF: 0.312 AC: 9357 AN: 30000

GnomAD4 genome AF: 0.265 AC: 40338 AN: 152050 Hom.: 6096 Cov.: 32 AF XY: 0.262 AC XY: 19459 AN XY: 74300

African (AFR) AF: 0.127 AC: 5253 AN: 41506

American (AMR) AF: 0.254 AC: 3869 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1524 AN: 3468

East Asian (EAS) AF: 0.203 AC: 1051 AN: 5186

South Asian (SAS) AF: 0.224 AC: 1078 AN: 4822

European-Finnish (FIN) AF: 0.316 AC: 3336 AN: 10542

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22883 AN: 67952

Other (OTH) AF: 0.328 AC: 692 AN: 2110

Alfa AF: 0.319 Hom.: 30421

Bravo AF: 0.256

Asia WGS AF: 0.227 AC: 792 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.72
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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: rs17256082; hg19: chr2-175292364;