chrX-65528279-C-T

Variant names:

• chrX-65528279-C-T
• rs745313876
• NM_031206.7:c.937G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_031206.7(LAS1L):​c.937G>A​(p.Gly313Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000693 in 1,197,312 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 29 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000071 (0 hom. 29 hem.)
• Consequence: LAS1L NM_031206.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.594
• 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04775563).
• BS2: High Hemizygotes in GnomAdExome4 at 29 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAS1L	NM_031206.7	MANE Select	c.937G>A	p.Gly313Ser	missense	Exon 7 of 14	NP_112483.1	Q9Y4W2-1
	LAS1L	NM_001375328.1		c.937G>A	p.Gly313Ser	missense	Exon 7 of 14	NP_001362257.1
	LAS1L	NM_001170649.2		c.937G>A	p.Gly313Ser	missense	Exon 7 of 13	NP_001164120.1	Q9Y4W2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAS1L	ENST00000374811.8	TSL:1 MANE Select	c.937G>A	p.Gly313Ser	missense	Exon 7 of 14	ENSP00000363944.3	Q9Y4W2-1
	LAS1L	ENST00000374807.9	TSL:1	c.937G>A	p.Gly313Ser	missense	Exon 7 of 13	ENSP00000363940.5	Q9Y4W2-2
	LAS1L	ENST00000867035.1		c.937G>A	p.Gly313Ser	missense	Exon 7 of 14	ENSP00000537094.1

Frequencies

GnomAD3 genomes AF: 0.0000533 AC: 6 AN: 112505 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: 0.000113

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000297 AC: 5 AN: 168168 AF XY: 0.0000545

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: 0.0000679

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000710 AC: 77 AN: 1084807 Hom.: 0 Cov.: 27 AF XY: 0.0000824 AC XY: 29 AN XY: 351819

African (AFR) AF: 0.00 AC: 0 AN: 26107

American (AMR) AF: 0.00 AC: 0 AN: 34656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19227

East Asian (EAS) AF: 0.00 AC: 0 AN: 29978

South Asian (SAS) AF: 0.00 AC: 0 AN: 52877

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40161

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3908

European-Non Finnish (NFE) AF: 0.0000709 AC: 59 AN: 832257

Other (OTH) AF: 0.000394 AC: 18 AN: 45636

GnomAD4 genome AF: 0.0000533 AC: 6 AN: 112505 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34665

African (AFR) AF: 0.00 AC: 0 AN: 30939

American (AMR) AF: 0.00 AC: 0 AN: 10655

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3593

South Asian (SAS) AF: 0.00 AC: 0 AN: 2763

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6225

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.000113 AC: 6 AN: 53246

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000378

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

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
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.92	L
PhyloP100		0.59
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.039
Sift	Benign	0.72	T
Sift4G	Benign	0.11	T
Polyphen		0.0030	B
Vest4		0.10
MutPred		0.27		Loss of loop (P = 0.0128)
MVP		0.43
MPC		0.63
ClinPred		0.063	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.067
gMVP		0.26
Mutation Taster		=97/3	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: rs745313876; hg19: chrX-64748159;