Variant chr16-48361616-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003031.4(SIAH1):c.813C>T(p.Gly271Gly) 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

SIAH1 links:

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]

LONP2 links:

LONP2 (HGNC:):

LONP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.24 with no splicing effect.

BA1

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	Protein	UniProt
SIAH1	NM_003031.4 linkuse as main transcript	c.813C>T	p.Gly271Gly	synonymous_variant	2/2	ENST00000394725.3	NP_003022.3	Q8IUQ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIAH1	ENST00000394725.3 linkuse as main transcript	c.813C>T	p.Gly271Gly	synonymous_variant	2/2	1	NM_003031.4	ENSP00000378214.2		Q8IUQ4-1

Frequencies

GnomAD3 genomes

AF:

0.0168

AC:

2550

AN:

152142

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.0168

AC:

2555

AN:

152260

Hom.:

Cov.:

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.:

Bravo

AF:

0.0194

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over