Genetic Variant NM_013243.4:c.160A>T (chr15-51683103-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_013243.4(SCG3):c.160A>T(p.Ile54Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,610,624 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

SCG3
NM_013243.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

Publications

0 publications found

Variant links:

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]

SCG3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019589335).

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.160A>T	p.Ile54Phe	missense	Exon 3 of 12	NP_037375.2
	SCG3	NM_001165257.2		c.-537A>T		5_prime_UTR	Exon 2 of 11	NP_001158729.1	Q8WXD2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCG3	ENST00000220478.8	TSL:1 MANE Select	c.160A>T	p.Ile54Phe	missense	Exon 3 of 12	ENSP00000220478.3	Q8WXD2-1
SCG3	ENST00000919610.1		c.160A>T	p.Ile54Phe	missense	Exon 3 of 12	ENSP00000589669.1
SCG3	ENST00000919607.1		c.160A>T	p.Ile54Phe	missense	Exon 3 of 12	ENSP00000589666.1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000218

AC:

AN:

247760

AF XY:

0.000127

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000411

AC:

AN:

1458278

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

725688

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33108

American (AMR)

AF:

0.00135

AC:

AN:

43586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25982

East Asian (EAS)

AF:

0.00

AC:

AN:

39628

South Asian (SAS)

AF:

0.00

AC:

AN:

85932

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53352

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110768

Other (OTH)

AF:

0.0000166

AC:

AN:

60206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41588

American (AMR)

AF:

0.000588

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.000181

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.084

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.78

M_CAP

Benign

0.0065

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

3.3

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.3

REVEL

Benign

0.048

Sift

Uncertain

0.012

Sift4G

Uncertain

0.053

Polyphen

0.57

Vest4

0.24

MutPred

0.19

Gain of methylation at K53 (P = 0.0391)

MVP

0.072

MPC

0.35

ClinPred

0.11

GERP RS

6.1

Varity_R

0.20

gMVP

0.24

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over