16-48362279-C-T

Position:

chr16-48362279-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003031.4(SIAH1):c.150G>A(p.Pro50Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,614,108 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 43 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 46 hom. )

Consequence

SIAH1
NM_003031.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.347

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=-0.51).

BP6

Variant 16-48362279-C-T is Benign according to our data. Variant chr16-48362279-C-T is described in ClinVar as [Benign]. Clinvar id is 779016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.347 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2029/152216) while in subpopulation AFR AF= 0.0425 (1764/41516). AF 95% confidence interval is 0.0408. There are 43 homozygotes in gnomad4. There are 996 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2029 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIAH1	NM_003031.4 linkuse as main transcript	c.150G>A	p.Pro50Pro	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.150G>A	p.Pro50Pro	synonymous_variant	2/2	1	NM_003031.4	ENSP00000378214.2		Q8IUQ4-1

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

2006

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0420

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.0290

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00815

GnomAD3 exomes

AF:

0.00548

AC:

1378

AN:

251482

Hom.:

AF XY:

0.00459

AC XY:

624

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0433

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.000694

Gnomad EAS exome

AF:

0.0282

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00182

AC:

2659

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1182

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0416

Gnomad4 AMR exome

AF:

0.00295

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.0175

Gnomad4 SAS exome

AF:

0.000742

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.0000791

Gnomad4 OTH exome

AF:

0.00439

GnomAD4 genome

AF:

0.0133

AC:

2029

AN:

152216

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

996

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0425

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.0289

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00587

Hom.:

Bravo

AF:

0.0149

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 30, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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