NM_024583.5:c.761T>A

Variant names:

• chr2-174422891-T-A
• rs139815824
• NM_024583.5:c.761T>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024583.5(SCRN3):​c.761T>A​(p.Ile254Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000069 in 1,449,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: SCRN3 NM_024583.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.32

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCRN3	NM_024583.5	c.761T>A	p.Ile254Lys	missense_variant	Exon 6 of 8	ENST00000272732.11	NP_078859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCRN3	ENST00000272732.11	c.761T>A	p.Ile254Lys	missense_variant	Exon 6 of 8	1	NM_024583.5	ENSP00000272732.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000800 AC: 2 AN: 250004 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135254

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000690 AC: 10 AN: 1449920 Hom.: 0 Cov.: 28 AF XY: 0.00000415 AC XY: 3 AN XY: 722106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000908

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	27
DANN	Benign	0.96
DEOGEN2	Benign	0.15	.;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.3	.;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.27
Sift	Benign	0.056	T;T
Sift4G	Uncertain	0.0030	D;T
Polyphen		0.97	.;D
Vest4		0.72
MutPred		0.66		.;Gain of disorder (P = 0.002);
MVP		0.29
MPC		0.23
ClinPred		0.92	D
GERP RS		5.4
Varity_R		0.74
gMVP		0.95

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

Publications

LitVar

Other links and lift over

dbSNP: rs139815824; hg19: chr2-175287619;