dbSNP rs761061736: LAS1L:p.Ser457Ser (chrX-65523637-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_031206.7(LAS1L):c.1371C>T(p.Ser457Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000617 in 1,198,493 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000066 ( 0 hom. 27 hem. )

Consequence

LAS1L
NM_031206.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.156

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant X-65523637-G-A is Benign according to our data. Variant chrX-65523637-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 464821.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.156 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 27 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAS1L	NM_031206.7 link	c.1371C>T	p.Ser457Ser	synonymous_variant	Exon 11 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.1371C>T	p.Ser457Ser	synonymous_variant	Exon 11 of 14	1	NM_031206.7	ENSP00000363944.3		Q9Y4W2-1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112492

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000572

AC:

AN:

157265

AF XY:

0.000104

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:

0.000133

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000663

AC:

AN:

1086001

Hom.:

Cov.:

AF XY:

0.0000763

AC XY:

AN XY:

353889

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26200

American (AMR)

AF:

0.00

AC:

AN:

33891

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19089

East Asian (EAS)

AF:

0.00

AC:

AN:

29702

South Asian (SAS)

AF:

0.00

AC:

AN:

52130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39596

Middle Eastern (MID)

AF:

0.000491

AC:

AN:

4072

European-Non Finnish (NFE)

AF:

0.0000778

AC:

AN:

835680

Other (OTH)

AF:

0.000110

AC:

AN:

45641

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.0000178

AC:

AN:

112492

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34640

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30964

American (AMR)

AF:

0.00

AC:

AN:

10692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3575

South Asian (SAS)

AF:

0.00

AC:

AN:

2726

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6197

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000376

AC:

AN:

53249

Other (OTH)

AF:

0.00

AC:

AN:

1510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000453

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Wilson-Turner syndrome

Benign:1

Sep 30, 2020

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

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.4

(source)

DANN

Benign

0.61

PhyloP100

-0.16

PromoterAI

-0.16

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over