chr11-125893851-C-T

Variant names:

• chr11-125893851-C-T
• rs3088241
• NM_031307.4:c.1380G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_031307.4(PUS3):​c.1380G>A​(p.Glu460Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 0.0 (0 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: PUS3 NM_031307.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 28 publications found

Genes affected

PUS3 (HGNC:25461): (pseudouridine synthase 3) The protein encoded by this gene catalyzes the formation of tRNA pseudouridine from tRNA uridine at position 39 in the anticodon stem and loop of transfer RNAs. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

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]

HYLS1 Gene-Disease associations (from GenCC):

• hydrolethalus syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• hydrolethalus syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-0.008 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031307.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUS3	NM_031307.4	MANE Select	c.1380G>A	p.Glu460Glu	synonymous	Exon 4 of 4	NP_112597.4
	HYLS1	NM_001134793.2	MANE Select	c.-26+2379C>T		intron	N/A	NP_001128265.1
	PUS3	NM_001441237.1		c.1380G>A	p.Glu460Glu	synonymous	Exon 5 of 5	NP_001428166.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUS3	ENST00000227474.8	TSL:1 MANE Select	c.1380G>A	p.Glu460Glu	synonymous	Exon 4 of 4	ENSP00000227474.3
	PUS3	ENST00000530811.5	TSL:1	c.1380G>A	p.Glu460Glu	synonymous	Exon 3 of 3	ENSP00000432386.1
	HYLS1	ENST00000425380.7	TSL:3 MANE Select	c.-26+2379C>T		intron	N/A	ENSP00000414884.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151828 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 39

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151828 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74106

African (AFR) AF: 0.00 AC: 0 AN: 41312

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 13827

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.3
DANN	Benign	0.60
PhyloP100		-0.0080

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

Other links and lift over

dbSNP: rs3088241; hg19: chr11-125763746;