chrX-65518120-TTCA-T

Variant names:

• chrX-65518120-TTCA-T
• rs750470319
• NM_031206.7:c.1791_1793delTGA

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_031206.7(LAS1L):​c.1791_1793delTGA​(p.Asp597del) variant causes a disruptive 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 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.49
• Publications: 1 publications found

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]

LAS1L Gene-Disease associations (from GenCC):

• Wilson-Turner syndrome

  Inheritance: XL Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
• spinal muscular atrophy with respiratory distress type 2

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_031206.7
• BP6: Variant X-65518120-TTCA-T is Benign according to our data. Variant chrX-65518120-TTCA-T is described in ClinVar as Benign. ClinVar VariationId is 533410.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 55 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAS1L	NM_031206.7	c.1791_1793delTGA	p.Asp597del	disruptive_inframe_deletion	Exon 12 of 14	ENST00000374811.8	NP_112483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAS1L	ENST00000374811.8	c.1791_1793delTGA	p.Asp597del	disruptive_inframe_deletion	Exon 12 of 14	1	NM_031206.7	ENSP00000363944.3

Frequencies

GnomAD3 genomes AF: 0.00196 AC: 219 AN: 111975 Hom.: 0 Cov.: 24

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

GnomAD2 exomes AF: 0.000549 AC: 99 AN: 180466 AF XY: 0.000407

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 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

African (AFR) AF: 0.00799 AC: 209 AN: 26166

American (AMR) AF: 0.000284 AC: 10 AN: 35181

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19295

East Asian (EAS) AF: 0.00 AC: 0 AN: 30161

South Asian (SAS) AF: 0.0000372 AC: 2 AN: 53796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40498

Middle Eastern (MID) AF: 0.000973 AC: 4 AN: 4110

European-Non Finnish (NFE) AF: 0.0000373 AC: 31 AN: 830442

Other (OTH) AF: 0.000701 AC: 32 AN: 45664

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

African (AFR) AF: 0.00665 AC: 205 AN: 30845

American (AMR) AF: 0.000471 AC: 5 AN: 10609

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3571

South Asian (SAS) AF: 0.000375 AC: 1 AN: 2670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6103

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000113 AC: 6 AN: 53140

Other (OTH) AF: 0.00260 AC: 4 AN: 1537

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, single submitter

Submissions by phenotype

Wilson-Turner syndrome Benign:1

Dec 11, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

LAS1L-related disorder Benign:1

Dec 15, 2023

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=81/19	polymorphism (auto)

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

Other links and lift over

dbSNP: rs750470319; hg19: chrX-64738000;