rs1338913054

Variant names:

• chr2-174399926-C-A
• rs1338913054
• NM_024583.5:c.164C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-174399926-C-A
• chr2-174399926-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_024583.5(SCRN3):​c.164C>A​(p.Thr55Lys) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000057 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCRN3 NM_024583.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.85
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024583.5. 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
	SCRN3	NM_024583.5	MANE Select	c.164C>A	p.Thr55Lys	missense	Exon 3 of 8	NP_078859.2
	SCRN3	NM_001412210.1		c.224C>A	p.Thr75Lys	missense	Exon 3 of 8	NP_001399139.1
	SCRN3	NM_001412202.1		c.164C>A	p.Thr55Lys	missense	Exon 3 of 8	NP_001399131.1	Q0VDG4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCRN3	ENST00000272732.11	TSL:1 MANE Select	c.164C>A	p.Thr55Lys	missense	Exon 3 of 8	ENSP00000272732.6	Q0VDG4-1
	SCRN3	ENST00000877601.1		c.164C>A	p.Thr55Lys	missense	Exon 3 of 8	ENSP00000547660.1
	SCRN3	ENST00000877602.1		c.164C>A	p.Thr55Lys	missense	Exon 3 of 8	ENSP00000547661.1

Frequencies

GnomAD3 genomes AF: 0.0000153 AC: 2 AN: 131124 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000238

Gnomad FIN AF: 0.000167

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000575 AC: 68 AN: 1183408 Hom.: 0 Cov.: 29 AF XY: 0.0000626 AC XY: 37 AN XY: 591000

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000437 AC: 1 AN: 22896

American (AMR) AF: 0.00 AC: 0 AN: 21648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20642

East Asian (EAS) AF: 0.00 AC: 0 AN: 31050

South Asian (SAS) AF: 0.0000662 AC: 4 AN: 60396

European-Finnish (FIN) AF: 0.0000207 AC: 1 AN: 48382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4696

European-Non Finnish (NFE) AF: 0.0000660 AC: 61 AN: 924650

Other (OTH) AF: 0.0000204 AC: 1 AN: 49048

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000152 AC: 2 AN: 131182 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 61842

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 34002

American (AMR) AF: 0.00 AC: 0 AN: 12142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3360

East Asian (EAS) AF: 0.00 AC: 0 AN: 4692

South Asian (SAS) AF: 0.000239 AC: 1 AN: 4184

European-Finnish (FIN) AF: 0.000167 AC: 1 AN: 5976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63994

Other (OTH) AF: 0.00 AC: 0 AN: 1742

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	2.0	M
PhyloP100		7.8
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.60		Loss of sheet (P = 0.0043)
MVP		0.43
MPC		0.23
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.93
gMVP		0.92
Mutation Taster		=20/80	disease causing

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: rs1338913054; hg19: chr2-175264654;