rs144560954

Variant names:

• chrX-65534557-C-T
• rs144560954
• NM_031206.7:c.159G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_031206.7(LAS1L):​c.159G>A​(p.Gln53Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000828 in 1,207,081 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.000045 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000046 (0 hom. 1 hem.)
• Consequence: LAS1L NM_031206.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.884
• Publications: 0 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant X-65534557-C-T is Benign according to our data. Variant chrX-65534557-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 533409.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.884 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAS1L	NM_031206.7	MANE Select	c.159G>A	p.Gln53Gln	synonymous	Exon 1 of 14	NP_112483.1
	LAS1L	NM_001375328.1		c.159G>A	p.Gln53Gln	synonymous	Exon 1 of 14	NP_001362257.1
	LAS1L	NM_001170649.2		c.159G>A	p.Gln53Gln	synonymous	Exon 1 of 13	NP_001164120.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAS1L	ENST00000374811.8	TSL:1 MANE Select	c.159G>A	p.Gln53Gln	synonymous	Exon 1 of 14	ENSP00000363944.3
	LAS1L	ENST00000374807.9	TSL:1	c.159G>A	p.Gln53Gln	synonymous	Exon 1 of 13	ENSP00000363940.5
	LAS1L	ENST00000867035.1		c.159G>A	p.Gln53Gln	synonymous	Exon 1 of 14	ENSP00000537094.1

Frequencies

GnomAD3 genomes AF: 0.0000446 AC: 5 AN: 112082 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000162

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

GnomAD2 exomes AF: 0.0000230 AC: 4 AN: 173751 AF XY: 0.00

Gnomad AFR exome AF: 0.000324

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000457 AC: 5 AN: 1094999 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 1 AN XY: 360717

African (AFR) AF: 0.000152 AC: 4 AN: 26349

American (AMR) AF: 0.00 AC: 0 AN: 34947

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19301

East Asian (EAS) AF: 0.00 AC: 0 AN: 30117

South Asian (SAS) AF: 0.00 AC: 0 AN: 53495

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 840507

Other (OTH) AF: 0.00 AC: 0 AN: 45975

GnomAD4 genome AF: 0.0000446 AC: 5 AN: 112082 Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1 AN XY: 34228

African (AFR) AF: 0.000162 AC: 5 AN: 30854

American (AMR) AF: 0.00 AC: 0 AN: 10592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3560

South Asian (SAS) AF: 0.00 AC: 0 AN: 2709

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53171

Other (OTH) AF: 0.00 AC: 0 AN: 1509

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000869

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Wilson-Turner syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.95
PhyloP100		0.88
PromoterAI		-0.022	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs144560954; hg19: chrX-64754437;