11-125891423-G-GTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001134793.2(HYLS1):c.-66_-65dup variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (45797 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: HYLS1 NM_001134793.2 splice_region, 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B: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 Benign. Variant got -10 ACMG points.

• BP6: Variant 11-125891423-G-GTT is Benign according to our data. Variant chr11-125891423-G-GTT is described in ClinVar as [Benign]. Clinvar id is 303351.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYLS1	NM_001134793.2	c.-66_-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.-66_-65dup		splice_region_variant, 5_prime_UTR_variant	2/3	3	NM_001134793.2	P1
HYLS1	ENST00000356438.7	c.-121_-120dup		splice_region_variant, 5_prime_UTR_variant	2/4	5		P1
HYLS1	ENST00000526028.1	c.-66_-65dup		splice_region_variant, 5_prime_UTR_variant	2/3	5		P1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 111277 AN: 135682 Hom.: 45791 Cov.: 0

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.817

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: 0.820 AC: 111287 AN: 135696 Hom.: 45797 Cov.: 0 AF XY: 0.820 AC XY: 52904 AN XY: 64500

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.890

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.861

Gnomad4 FIN AF: 0.841

Gnomad4 NFE AF: 0.871

Gnomad4 OTH AF: 0.818

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hydrolethalus syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;