2-174398366-A-G

Position:

• chr2-174398366-A-G

Variant summary

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

The NM_024583.5(SCRN3):​c.83A>G​(p.Asp28Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCRN3 NM_024583.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.19

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, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCRN3	NM_024583.5	c.83A>G	p.Asp28Gly	missense_variant	2/8	ENST00000272732.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCRN3	ENST00000272732.11	c.83A>G	p.Asp28Gly	missense_variant	2/8	1	NM_024583.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

The c.83A>G (p.D28G) alteration is located in exon 2 (coding exon 1) of the SCRN3 gene. This alteration results from a A to G substitution at nucleotide position 83, causing the aspartic acid (D) at amino acid position 28 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T;.;T;T;.;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;T;D;D;D;D
M_CAP	Benign	0.077	D
MetaRNN	Pathogenic	0.77	D;D;D;D;D;D
MetaSVM	Benign	-0.60	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.6	D;D;D;D;D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.010	D;D;D;D;D;D
Sift4G	Benign	0.069	T;D;D;D;T;T
Polyphen		1.0	.;.;D;.;.;.
Vest4		0.67, 0.89
MutPred		0.67		Loss of stability (P = 0.0421);.;Loss of stability (P = 0.0421);Loss of stability (P = 0.0421);Loss of stability (P = 0.0421);Loss of stability (P = 0.0421);
MVP		0.34
MPC		0.25
ClinPred		0.99	D
GERP RS		6.1
Varity_R		0.62
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.38		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-175263094;