dbSNP rs1057518699: LAS1L:p.Arg415Trp (chrX-65524113-G-A) – ACMG Classification: Uncertain_significance (5 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate

The NM_031206.7(LAS1L):c.1243C>T(p.Arg415Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 23)

Consequence

LAS1L
NM_031206.7 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:3

Conservation

PhyloP100: 4.38

Publications

4 publications found

Variant links:

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

LAS1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.809

PP5

Variant X-65524113-G-A is Pathogenic according to our data. Variant chrX-65524113-G-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 374326.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAS1L	NM_031206.7	MANE Select	c.1243C>T	p.Arg415Trp	missense	Exon 10 of 14	NP_112483.1	Q9Y4W2-1
LAS1L	NM_001375328.1		c.1243C>T	p.Arg415Trp	missense	Exon 10 of 14	NP_001362257.1
LAS1L	NM_001170649.2		c.1192C>T	p.Arg398Trp	missense	Exon 9 of 13	NP_001164120.1	Q9Y4W2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAS1L	ENST00000374811.8	TSL:1 MANE Select	c.1243C>T	p.Arg415Trp	missense	Exon 10 of 14	ENSP00000363944.3	Q9Y4W2-1
LAS1L	ENST00000374807.9	TSL:1	c.1192C>T	p.Arg398Trp	missense	Exon 9 of 13	ENSP00000363940.5	Q9Y4W2-2
LAS1L	ENST00000867035.1		c.1285C>T	p.Arg429Trp	missense	Exon 10 of 14	ENSP00000537094.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Likely pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Wilson-Turner syndrome (2)

Global developmental delay (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.42

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.42

MetaRNN

Pathogenic

0.81

MetaSVM

Benign

-0.38

MutationAssessor

Uncertain

2.9

PhyloP100

4.4

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.37

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.67

MutPred

0.63

Gain of helix (P = 0.0325)

MVP

0.69

MPC

1.6

ClinPred

1.0

GERP RS

4.8

PromoterAI

-0.044

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.41

gMVP

0.89

Mutation Taster

=8/92

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over