NM_003469.5:c.407C>T

Variant names:

• chr2-223598876-G-A
• NM_003469.5:c.407C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003469.5(SCG2):​c.407C>T​(p.Ala136Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCG2 NM_003469.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05
• Publications: 0 publications found

Genes affected

SCG2 (HGNC:10575): (secretogranin II) The protein encoded by this gene is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins. Studies in rodents suggest that the full-length protein, secretogranin II, is involved in the packaging or sorting of peptide hormones and neuropeptides into secretory vesicles. The full-length protein is cleaved to produce the active peptide secretoneurin, which exerts chemotaxic effects on specific cell types, and EM66, whose function is unknown. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042022318).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003469.5. 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
	SCG2	NM_003469.5	MANE Select	c.407C>T	p.Ala136Val	missense	Exon 2 of 2	NP_003460.2	P13521

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCG2	ENST00000305409.3	TSL:1 MANE Select	c.407C>T	p.Ala136Val	missense	Exon 2 of 2	ENSP00000304133.2	P13521
	SCG2	ENST00000421386.1	TSL:3	c.407C>T	p.Ala136Val	missense	Exon 2 of 2	ENSP00000394702.1	C9JQI2
	SCG2	ENST00000433889.1	TSL:4	c.*30C>T		downstream_gene	N/A	ENSP00000415468.1	C9JDT0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Benign	0.076
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.67
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.9	M
PhyloP100		1.0
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.054
Sift	Benign	0.25	T
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.22		Loss of phosphorylation at S139 (P = 0.1596)
MVP		0.12
MPC		0.063
ClinPred		0.051	T
GERP RS		1.6
Varity_R		0.039
gMVP		0.099
Mutation Taster		=95/5	polymorphism

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

hg19: chr2-224463594;