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16-48361616-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003031.4(SIAH1):c.813C>T(p.Gly271=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,612,908 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 59 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 60 hom. )

Consequence

SIAH1
NM_003031.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.24
Variant links:
Genes affected
SIAH1 (HGNC:10857): (siah E3 ubiquitin protein ligase 1) This gene encodes a protein that is a member of the seven in absentia homolog (SIAH) family. The protein is an E3 ligase and is involved in ubiquitination and proteasome-mediated degradation of specific proteins. The activity of this ubiquitin ligase has been implicated in the development of certain forms of Parkinson's disease, the regulation of the cellular response to hypoxia and induction of apoptosis. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008]
LONP2 (HGNC:20598): (lon peptidase 2, peroxisomal) In human, peroxisomes function primarily to catalyze fatty acid beta-oxidation and, as a by-product, produce hydrogen peroxide and superoxide. The protein encoded by this gene is an ATP-dependent protease that likely plays a role in maintaining overall peroxisome homeostasis as well as proteolytically degrading peroxisomal proteins damaged by oxidation. The protein has an N-terminal Lon N substrate recognition domain, an ATPase domain, a proteolytic domain, and, in some isoforms, a C-terminal peroxisome targeting sequence. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2017]

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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=-0.56).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-48361616-G-A is Benign according to our data. Variant chr16-48361616-G-A is described in ClinVar as [Benign]. Clinvar id is 773056.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=3.24 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SIAH1NM_003031.4 linkuse as main transcriptc.813C>T p.Gly271= synonymous_variant 2/2 ENST00000394725.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIAH1ENST00000394725.3 linkuse as main transcriptc.813C>T p.Gly271= synonymous_variant 2/21 NM_003031.4 P4Q8IUQ4-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0168
AC:
2550
AN:
152142
Hom.:
59
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0566
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00969
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.0134
GnomAD3 exomes
AF:
0.00457
AC:
1148
AN:
251336
Hom.:
24
AF XY:
0.00349
AC XY:
474
AN XY:
135872
show subpopulations
Gnomad AFR exome
AF:
0.0581
Gnomad AMR exome
AF:
0.00393
Gnomad ASJ exome
AF:
0.000298
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000261
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000308
Gnomad OTH exome
AF:
0.00359
GnomAD4 exome
AF:
0.00190
AC:
2772
AN:
1460648
Hom.:
60
Cov.:
31
AF XY:
0.00166
AC XY:
1203
AN XY:
726376
show subpopulations
Gnomad4 AFR exome
AF:
0.0581
Gnomad4 AMR exome
AF:
0.00454
Gnomad4 ASJ exome
AF:
0.000191
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000359
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000228
Gnomad4 OTH exome
AF:
0.00474
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0168
AC:
2555
AN:
152260
Hom.:
59
Cov.:
32
AF XY:
0.0161
AC XY:
1195
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0566
Gnomad4 AMR
AF:
0.00968
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.0132
Alfa
AF:
0.00781
Hom.:
18
Bravo
AF:
0.0194
Asia WGS
AF:
0.00433
AC:
16
AN:
3478
EpiCase
AF:
0.000436
EpiControl
AF:
0.000356

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 testingInvitaeMar 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
Cadd
Benign
9.0
Dann
Benign
0.85

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: rs35374298; hg19: chr16-48395527; API