rs745313876

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.594

Publications

0 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: 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

LAS1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAS1L	NM_031206.7 link	c.937G>A	p.Gly313Ser	missense_variant	Exon 7 of 14	ENST00000374811.8	NP_112483.1	Q9Y4W2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAS1L	ENST00000374811.8 link	c.937G>A	p.Gly313Ser	missense_variant	Exon 7 of 14	1	NM_031206.7	ENSP00000363944.3		Q9Y4W2-1

Frequencies

GnomAD3 genomes

AF:

0.0000533

AC:

AN:

112505

Hom.:

Cov.:

show subpopulations

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:

AN:

168168

AF XY:

0.0000545

show subpopulations

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:

AN:

1084807

Hom.:

Cov.:

AF XY:

0.0000824

AC XY:

AN XY:

351819

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26107

American (AMR)

AF:

0.00

AC:

AN:

34656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19227

East Asian (EAS)

AF:

0.00

AC:

AN:

29978

South Asian (SAS)

AF:

0.00

AC:

AN:

52877

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40161

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3908

European-Non Finnish (NFE)

AF:

0.0000709

AC:

AN:

832257

Other (OTH)

AF:

0.000394

AC:

AN:

45636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000533

AC:

AN:

112505

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34665

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30939

American (AMR)

AF:

0.00

AC:

AN:

10655

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3593

South Asian (SAS)

AF:

0.00

AC:

AN:

2763

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6225

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53246

Other (OTH)

AF:

0.00

AC:

AN:

1513

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Wilson-Turner syndrome

Uncertain:1

Aug 24, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ClinVar contains an entry for this variant (Variation ID: 579081). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LAS1L protein function. This variant has not been reported in the literature in individuals affected with LAS1L-related conditions. This variant is present in population databases (rs745313876, gnomAD 0.007%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 313 of the LAS1L protein (p.Gly313Ser). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;T;.

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.81

T;T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.048

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.92

L;L;.

PhyloP100

0.59

PrimateAI

Benign

0.28

PROVEAN

Benign

0.44

N;N;N

REVEL

Benign

0.039

Sift

Benign

0.72

T;T;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.0030

B;B;B

Vest4

0.10

MutPred

0.27

Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);.;

MVP

0.43

MPC

0.63

ClinPred

0.063

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

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over