rs750470319

chrX-65518120-TTCA-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_031206.7(LAS1L):c.1791_1793del(p.Asp597del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000425 in 1,197,343 control chromosomes in the GnomAD database, including 1 homozygotes. There are 137 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., 55 hem., cov: 24)
  • Exomes 𝑓: 0.00027 (1 hom. 82 hem.)
• Consequence: LAS1L NM_031206.7 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.49

Genes affected

LAS1L (HGNC:25726): (LAS1 like ribosome biogenesis factor) Enables RNA binding activity. Predicted to be involved in maturation of 5.8S rRNA and maturation of LSU-rRNA. Located in membrane. Part of MLL1 complex. Implicated in Wilson-Turner syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant X-65518120-TTCA-T is Benign according to our data. Variant chrX-65518120-TTCA-T is described in ClinVar as [Benign]. Clinvar id is 533410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-65518120-TTCA-T is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd at 54 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAS1L	NM_031206.7	c.1791_1793del	p.Asp597del	inframe_deletion	12/14	ENST00000374811.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAS1L	ENST00000374811.8	c.1791_1793del	p.Asp597del	inframe_deletion	12/14	1	NM_031206.7	P2

Frequencies

GnomAD3 genomes AF: 0.00196 AC: 219 AN: 111975 Hom.: 0 Cov.: 24 AF XY: 0.00158 AC XY: 54 AN XY: 34159

Gnomad AFR AF: 0.00660

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000472

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000374

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000113

Gnomad OTH AF: 0.00263

GnomAD3 exomes AF: 0.000549 AC: 99 AN: 180466 Hom.: 1 AF XY: 0.000407 AC XY: 27 AN XY: 66394

Gnomad AFR exome AF: 0.00665

Gnomad AMR exome AF: 0.000256

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000377

Gnomad OTH exome AF: 0.000445

GnomAD4 exome AF: 0.000265 AC: 288 AN: 1085313 Hom.: 1 AF XY: 0.000234 AC XY: 82 AN XY: 351151

Gnomad4 AFR exome AF: 0.00799

Gnomad4 AMR exome AF: 0.000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000372

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000373

Gnomad4 OTH exome AF: 0.000701

GnomAD4 genome AF: 0.00197 AC: 221 AN: 112030 Hom.: 0 Cov.: 24 AF XY: 0.00161 AC XY: 55 AN XY: 34224

Gnomad4 AFR AF: 0.00665

Gnomad4 AMR AF: 0.000471

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000375

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000113

Gnomad4 OTH AF: 0.00260

Alfa AF: 0.00109 Hom.: 4

Bravo AF: 0.00240

Asia WGS AF: 0.000398 AC: 1 AN: 2522

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Wilson-Turner syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2023

- -

LAS1L-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 15, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs750470319; hg19: chrX-64738000;