rs992864125

Variant names:

• chrX-65532612-T-C
• rs992864125
• NM_031206.7:c.381A>G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_031206.7(LAS1L):​c.381A>G​(p.Ser127Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,083,406 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000015 (0 hom. 4 hem.)
• Consequence: LAS1L NM_031206.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.09

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-65532612-T-C is Benign according to our data. Variant chrX-65532612-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 464825.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.09 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAS1L	NM_031206.7	c.381A>G	p.Ser127Ser	synonymous_variant	Exon 3 of 14	ENST00000374811.8	NP_112483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAS1L	ENST00000374811.8	c.381A>G	p.Ser127Ser	synonymous_variant	Exon 3 of 14	1	NM_031206.7	ENSP00000363944.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.0000109 AC: 2 AN: 183218 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67662

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.0000148 AC: 16 AN: 1083406 Hom.: 0 Cov.: 27 AF XY: 0.0000114 AC XY: 4 AN XY: 351572

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000169

Gnomad4 OTH exome AF: 0.0000438

GnomAD4 genome Cov.: 24

Alfa AF: 0.000111 Hom.: 0

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Wilson-Turner syndrome Benign:1

Jun 27, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs992864125; hg19: chrX-64752492; COSMIC: COSV56706557;