dbSNP rs148989578: LAS1L:p.Val564Ala (chrX-65518223-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_031206.7(LAS1L):c.1691T>C(p.Val564Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,209,710 control chromosomes in the GnomAD database, including 1 homozygotes. There are 69 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., 33 hem., cov: 24)

Exomes 𝑓: 0.00012 ( 0 hom. 36 hem. )

Consequence

LAS1L
NM_031206.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.660

Publications

1 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029076338).

BP6

Variant X-65518223-A-G is Benign according to our data. Variant chrX-65518223-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 533408.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 33 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAS1L	NM_031206.7 link	c.1691T>C	p.Val564Ala	missense_variant	Exon 12 of 14	ENST00000374811.8	NP_112483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAS1L	ENST00000374811.8 link	c.1691T>C	p.Val564Ala	missense_variant	Exon 12 of 14	1	NM_031206.7	ENSP00000363944.3

Frequencies

GnomAD3 genomes

AF:

0.00136

AC:

152

AN:

111698

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000284

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:

0.000350

AC:

AN:

182790

AF XY:

0.000178

show subpopulations

Gnomad AFR exome

AF:

0.00395

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000722

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000122

AC:

134

AN:

1097959

Hom.:

Cov.:

AF XY:

0.0000991

AC XY:

AN XY:

363319

show subpopulations

African (AFR)

AF:

0.00439

AC:

116

AN:

26397

American (AMR)

AF:

0.0000284

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19384

East Asian (EAS)

AF:

0.000265

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54139

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40523

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

841883

Other (OTH)

AF:

0.000152

AC:

AN:

46086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.00135

AC:

151

AN:

111751

Hom.:

Cov.:

AF XY:

0.000971

AC XY:

AN XY:

33991

show subpopulations

African (AFR)

AF:

0.00481

AC:

148

AN:

30753

American (AMR)

AF:

0.000283

AC:

AN:

10590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3559

South Asian (SAS)

AF:

0.00

AC:

AN:

2663

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6045

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53073

Other (OTH)

AF:

0.00

AC:

AN:

1527

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000541

Hom.:

Bravo

AF:

0.00164

ESP6500AA

AF:

0.00548

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000387

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Wilson-Turner syndrome

Benign:1

Nov 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.38

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.019

.;T;.

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.57

T;T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

.;L;.

PhyloP100

-0.66

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.29

N;N;N

REVEL

Benign

0.041

Sift

Benign

0.82

T;T;T

Sift4G

Benign

0.61

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.031

MVP

0.27

MPC

0.76

ClinPred

0.0052

GERP RS

-6.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.051

gMVP

0.14

Mutation Taster

=100/0

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