11-125891483-G-GA

Position:

• chr11-125891483-G-GA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001134793.2(HYLS1):​c.-26+28dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2584 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: HYLS1 NM_001134793.2 intron
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.488

Genes affected

HYLS1 (HGNC:26558): (HYLS1 centriolar and ciliogenesis associated) This gene encodes a protein localized to the cytoplasm. Mutations in this gene are associated with hydrolethalus syndrome. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HYLS1	NM_001134793.2	c.-26+28dup		intron_variant		ENST00000425380.7	NP_001128265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HYLS1	ENST00000425380.7	c.-26+28dup		intron_variant		3	NM_001134793.2	ENSP00000414884	P1
HYLS1	ENST00000356438.7	c.-81+28dup		intron_variant		5		ENSP00000348815	P1
HYLS1	ENST00000526028.1	c.-26+28dup		intron_variant		5		ENSP00000436833	P1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 19732 AN: 107228 Hom.: 2586 Cov.: 0

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.200

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.194

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.184 AC: 19717 AN: 107210 Hom.: 2584 Cov.: 0 AF XY: 0.188 AC XY: 9132 AN XY: 48586

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.193

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hydrolethalus syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs11382127; hg19: chr11-125761378;