rs148989578

chrX-65518223-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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. 14/19 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.660

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 533408.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-65518223-A-G is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd at 34 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAS1L	NM_031206.7	c.1691T>C	p.Val564Ala	missense_variant	12/14	ENST00000374811.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAS1L	ENST00000374811.8	c.1691T>C	p.Val564Ala	missense_variant	12/14	1	NM_031206.7	P2

Frequencies

GnomAD3 genomes AF: 0.00136 AC: 152 AN: 111698 Hom.: 1 Cov.: 24 AF XY: 0.00100 AC XY: 34 AN XY: 33928

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

GnomAD3 exomes AF: 0.000350 AC: 64 AN: 182790 Hom.: 0 AF XY: 0.000178 AC XY: 12 AN XY: 67438

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 SAS exome AF: 0.00

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.: 0 Cov.: 31 AF XY: 0.0000991 AC XY: 36 AN XY: 363319

Gnomad4 AFR exome AF: 0.00439

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000265

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000238

Gnomad4 OTH exome AF: 0.000152

GnomAD4 genome AF: 0.00135 AC: 151 AN: 111751 Hom.: 1 Cov.: 24 AF XY: 0.000971 AC XY: 33 AN XY: 33991

Gnomad4 AFR AF: 0.00481

Gnomad4 AMR AF: 0.000283

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000184 Hom.: 6

Bravo AF: 0.00164

ESP6500AA AF: 0.00548 AC: 21

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000387 AC: 47

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Wilson-Turner syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.38
Dann	Benign	0.62
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.57	T;T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.0029	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.31	T
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	T
GERP RS		-6.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051
gMVP		0.14

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

LitVar

Other links and lift over

dbSNP: rs148989578; hg19: chrX-64738103;