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GeneBe

15-51683349-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_013243.4(SCG3):c.312T>C(p.Asn104=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,613,536 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 25 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 33 hom. )

Consequence

SCG3
NM_013243.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.387
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-51683349-T-C is Benign according to our data. Variant chr15-51683349-T-C is described in ClinVar as [Benign]. Clinvar id is 777461.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.387 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1588/152292) while in subpopulation AFR AF= 0.0367 (1526/41554). AF 95% confidence interval is 0.0352. There are 25 homozygotes in gnomad4. There are 715 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 25 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCG3NM_013243.4 linkuse as main transcriptc.312T>C p.Asn104= synonymous_variant 4/12 ENST00000220478.8
SCG3NM_001165257.2 linkuse as main transcriptc.-385T>C 5_prime_UTR_variant 3/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCG3ENST00000220478.8 linkuse as main transcriptc.312T>C p.Asn104= synonymous_variant 4/121 NM_013243.4 P1Q8WXD2-1
SCG3ENST00000542355.6 linkuse as main transcriptc.-385T>C 5_prime_UTR_variant 3/112 Q8WXD2-2
SCG3ENST00000558709.1 linkuse as main transcriptc.-242T>C 5_prime_UTR_variant 3/52

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0104
AC:
1579
AN:
152174
Hom.:
25
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0366
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00301
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:
0.00767
GnomAD3 exomes
AF:
0.00252
AC:
634
AN:
251232
Hom.:
8
AF XY:
0.00182
AC XY:
247
AN XY:
135798
show subpopulations
Gnomad AFR exome
AF:
0.0360
Gnomad AMR exome
AF:
0.00127
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.000653
GnomAD4 exome
AF:
0.00105
AC:
1530
AN:
1461244
Hom.:
33
Cov.:
30
AF XY:
0.000876
AC XY:
637
AN XY:
726942
show subpopulations
Gnomad4 AFR exome
AF:
0.0384
Gnomad4 AMR exome
AF:
0.00157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000810
Gnomad4 OTH exome
AF:
0.00252
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0104
AC:
1588
AN:
152292
Hom.:
25
Cov.:
32
AF XY:
0.00960
AC XY:
715
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0367
Gnomad4 AMR
AF:
0.00301
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00759
Alfa
AF:
0.00504
Hom.:
5
Bravo
AF:
0.0115
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
0.42
Dann
Benign
0.44

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35106685; hg19: chr15-51975546; API