X-65518022-C-T

Variant names:

• chrX-65518022-C-T
• rs371394378
• NM_031206.7:c.1892G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031206.7(LAS1L):​c.1892G>A​(p.Gly631Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 1,208,726 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G631A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.0000064 (0 hom. 1 hem.)
• Consequence: LAS1L NM_031206.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• 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: 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07197869).

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.1892G>A	p.Gly631Glu	missense	Exon 12 of 14	NP_112483.1	Q9Y4W2-1
	LAS1L	NM_001375328.1		c.1892G>A	p.Gly631Glu	missense	Exon 12 of 14	NP_001362257.1
	LAS1L	NM_001170649.2		c.1841G>A	p.Gly614Glu	missense	Exon 11 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.1892G>A	p.Gly631Glu	missense	Exon 12 of 14	ENSP00000363944.3	Q9Y4W2-1
	LAS1L	ENST00000374807.9	TSL:1	c.1841G>A	p.Gly614Glu	missense	Exon 11 of 13	ENSP00000363940.5	Q9Y4W2-2
	LAS1L	ENST00000867035.1		c.1934G>A	p.Gly645Glu	missense	Exon 12 of 14	ENSP00000537094.1

Frequencies

GnomAD3 genomes AF: 0.00000888 AC: 1 AN: 112632 Hom.: 0 Cov.: 24

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000565 AC: 1 AN: 176921 AF XY: 0.0000159

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: 0.0000128

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000639 AC: 7 AN: 1096094 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 361832

African (AFR) AF: 0.0000381 AC: 1 AN: 26245

American (AMR) AF: 0.00 AC: 0 AN: 34961

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19194

East Asian (EAS) AF: 0.00 AC: 0 AN: 30199

South Asian (SAS) AF: 0.00 AC: 0 AN: 53733

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40471

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4114

European-Non Finnish (NFE) AF: 0.00000713 AC: 6 AN: 841193

Other (OTH) AF: 0.00 AC: 0 AN: 45984

GnomAD4 genome AF: 0.00000888 AC: 1 AN: 112632 Hom.: 0 Cov.: 24 AF XY: 0.0000287 AC XY: 1 AN XY: 34786

African (AFR) AF: 0.00 AC: 0 AN: 31032

American (AMR) AF: 0.00 AC: 0 AN: 10695

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3592

South Asian (SAS) AF: 0.00 AC: 0 AN: 2737

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6217

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

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53259

Other (OTH) AF: 0.00 AC: 0 AN: 1527

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Uncertain	0.97
DEOGEN2	Benign	0.042	T
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.56	N
PhyloP100		1.6
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.022
Sift	Benign	0.11	T
Sift4G	Benign	0.35	T
Polyphen		0.24	B
Vest4		0.090
MVP		0.18
MPC		0.82
ClinPred		0.12	T
GERP RS		2.6
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.13
gMVP		0.28
Mutation Taster		=99/1	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: rs371394378; hg19: chrX-64737902;