15-51683369-C-T

Variant names:

• chr15-51683369-C-T
• rs150705817
• NM_013243.4:c.332C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_013243.4(SCG3):​c.332C>T​(p.Thr111Ile) 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. 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. T111S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCG3 NM_013243.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.04
• Publications: 2 publications found

Genes affected

SCG3 (HGNC:13707): (secretogranin III) The protein encoded by this gene is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins. Granins may serve as precursors for biologically active peptides. Some granins have been shown to function as helper proteins in sorting and proteolytic processing of prohormones; however, the function of this protein is unknown. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.79

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013243.4. 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
	SCG3	NM_013243.4	MANE Select	c.332C>T	p.Thr111Ile	missense	Exon 4 of 12	NP_037375.2
	SCG3	NM_001165257.2		c.-365C>T		5_prime_UTR	Exon 3 of 11	NP_001158729.1	Q8WXD2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCG3	ENST00000220478.8	TSL:1 MANE Select	c.332C>T	p.Thr111Ile	missense	Exon 4 of 12	ENSP00000220478.3	Q8WXD2-1
	SCG3	ENST00000919610.1		c.332C>T	p.Thr111Ile	missense	Exon 4 of 12	ENSP00000589669.1
	SCG3	ENST00000919607.1		c.332C>T	p.Thr111Ile	missense	Exon 4 of 12	ENSP00000589666.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251162 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.34	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.30		Loss of sheet (P = 0.0126)
MVP		0.23
MPC		0.64
ClinPred		0.99	D
GERP RS		6.1
Varity_R		0.84
gMVP		0.43

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: rs150705817; hg19: chr15-51975566;