rs9938490

Variant names:

• chr16-48414175-T-C
• rs9938490
• ENST00000568007.5:n.-532-10508A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000568007.5(SIAH1):​n.-532-10508A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,074 control chromosomes in the GnomAD database, including 3,957 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3957 hom., cov: 32)
• Consequence: SIAH1 ENST00000568007.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• Buratti-Harel syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIAH1	ENST00000568007.5	n.-532-10508A>G		intron_variant	Intron 1 of 6	1		ENSP00000456421.1
SIAH1	ENST00000567973.1	n.504+2641A>G		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31194 AN: 151956 Hom.: 3936 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.0769

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.205 AC: 31250 AN: 152074 Hom.: 3957 Cov.: 32 AF XY: 0.203 AC XY: 15077 AN XY: 74326

African (AFR) AF: 0.351 AC: 14570 AN: 41470

American (AMR) AF: 0.153 AC: 2334 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 618 AN: 3470

East Asian (EAS) AF: 0.0143 AC: 74 AN: 5180

South Asian (SAS) AF: 0.0757 AC: 365 AN: 4822

European-Finnish (FIN) AF: 0.167 AC: 1762 AN: 10578

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10882 AN: 67980

Other (OTH) AF: 0.195 AC: 411 AN: 2108

Alfa AF: 0.168 Hom.: 1214

Bravo AF: 0.210

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.40
DANN	Benign	0.50
PhyloP100		-1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9938490; hg19: chr16-48448086;