chr2-174404135-A-T

Variant names:

• chr2-174404135-A-T
• rs1023907399
• NM_024583.5:c.574A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024583.5(SCRN3):​c.574A>T​(p.Ile192Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I192V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCRN3 NM_024583.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.80
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29144862).

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.574A>T	p.Ile192Leu	missense	Exon 5 of 8	NP_078859.2
	SCRN3	NM_001412210.1		c.634A>T	p.Ile212Leu	missense	Exon 5 of 8	NP_001399139.1
	SCRN3	NM_001412202.1		c.574A>T	p.Ile192Leu	missense	Exon 5 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.574A>T	p.Ile192Leu	missense	Exon 5 of 8	ENSP00000272732.6	Q0VDG4-1
	SCRN3	ENST00000877601.1		c.574A>T	p.Ile192Leu	missense	Exon 5 of 8	ENSP00000547660.1
	SCRN3	ENST00000877602.1		c.574A>T	p.Ile192Leu	missense	Exon 5 of 8	ENSP00000547661.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461464 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727036

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111768

Other (OTH) AF: 0.0000166 AC: 1 AN: 60382

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.8
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.11
Sift	Benign	0.49	T
Sift4G	Benign	0.36	T
Polyphen		0.90	P
Vest4		0.47
MutPred		0.74		Loss of catalytic residue at I192 (P = 0.0257)
MVP		0.076
MPC		0.050
ClinPred		0.50	T
GERP RS		3.0
Varity_R		0.27
gMVP		0.84
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs1023907399; hg19: chr2-175268863;