X-65523637-G-A

Variant names:

• chrX-65523637-G-A
• rs761061736
• NM_031206.7:c.1371C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_031206.7(LAS1L):​c.1371C>T​(p.Ser457Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000617 in 1,198,493 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000066 (0 hom. 27 hem.)
• Consequence: LAS1L NM_031206.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.156
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-65523637-G-A is Benign according to our data. Variant chrX-65523637-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 464821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.156 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 27 Unknown,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031206.7. 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
	LAS1L	NM_031206.7	MANE Select	c.1371C>T	p.Ser457Ser	synonymous	Exon 11 of 14	NP_112483.1
	LAS1L	NM_001375328.1		c.1371C>T	p.Ser457Ser	synonymous	Exon 11 of 14	NP_001362257.1
	LAS1L	NM_001170649.2		c.1320C>T	p.Ser440Ser	synonymous	Exon 10 of 13	NP_001164120.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAS1L	ENST00000374811.8	TSL:1 MANE Select	c.1371C>T	p.Ser457Ser	synonymous	Exon 11 of 14	ENSP00000363944.3
	LAS1L	ENST00000374807.9	TSL:1	c.1320C>T	p.Ser440Ser	synonymous	Exon 10 of 13	ENSP00000363940.5
	LAS1L	ENST00000374804.9	TSL:2	c.1194C>T	p.Ser398Ser	synonymous	Exon 9 of 12	ENSP00000363937.5

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112492 Hom.: 0 Cov.: 23

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: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000572 AC: 9 AN: 157265 AF XY: 0.000104

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000663 AC: 72 AN: 1086001 Hom.: 0 Cov.: 30 AF XY: 0.0000763 AC XY: 27 AN XY: 353889

African (AFR) AF: 0.00 AC: 0 AN: 26200

American (AMR) AF: 0.00 AC: 0 AN: 33891

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19089

East Asian (EAS) AF: 0.00 AC: 0 AN: 29702

South Asian (SAS) AF: 0.00 AC: 0 AN: 52130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39596

Middle Eastern (MID) AF: 0.000491 AC: 2 AN: 4072

European-Non Finnish (NFE) AF: 0.0000778 AC: 65 AN: 835680

Other (OTH) AF: 0.000110 AC: 5 AN: 45641

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112492 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34640

African (AFR) AF: 0.00 AC: 0 AN: 30964

American (AMR) AF: 0.00 AC: 0 AN: 10692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.00 AC: 0 AN: 2726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6197

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53249

Other (OTH) AF: 0.00 AC: 0 AN: 1510

Alfa AF: 0.000130 Hom.: 1

Bravo AF: 0.0000453

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Wilson-Turner syndrome Benign:1

Sep 30, 2020

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.61
PhyloP100		-0.16
PromoterAI		-0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs761061736; hg19: chrX-64743517; COSMIC: COSV56709369; COSMIC: COSV56709369;