11-125891423-G-GT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001134793.2(HYLS1):c.-65dup variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (2 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: HYLS1 NM_001134793.2 splice_region, 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.440

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYLS1	NM_001134793.2	c.-65dup		splice_region_variant, 5_prime_UTR_variant	2/3	ENST00000425380.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYLS1	ENST00000425380.7	c.-65dup		splice_region_variant, 5_prime_UTR_variant	2/3	3	NM_001134793.2	P1
HYLS1	ENST00000356438.7	c.-120dup		splice_region_variant, 5_prime_UTR_variant	2/4	5		P1
HYLS1	ENST00000526028.1	c.-65dup		splice_region_variant, 5_prime_UTR_variant	2/3	5		P1

Frequencies

GnomAD3 genomes AF: 0.00173 AC: 235 AN: 135798 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00115

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00585

Gnomad EAS AF: 0.000208

Gnomad SAS AF: 0.000455

Gnomad FIN AF: 0.00125

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00197

Gnomad OTH AF: 0.00165

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: 0.00173 AC: 235 AN: 135812 Hom.: 2 Cov.: 0 AF XY: 0.00152 AC XY: 98 AN XY: 64564

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00585

Gnomad4 EAS AF: 0.000208

Gnomad4 SAS AF: 0.000458

Gnomad4 FIN AF: 0.00125

Gnomad4 NFE AF: 0.00197

Gnomad4 OTH AF: 0.00164

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hydrolethalus syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs60408033; hg19: chr11-125761318;