rs779407196

Variant names:

• chrX-65534617-C-G
• rs779407196
• NM_031206.7:c.99G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-65534617-C-G
• chrX-65534617-C-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_031206.7(LAS1L):​c.99G>C​(p.Ser33Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,198,809 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 71 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 0.000072 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.00026 (0 hom. 69 hem.)
• Consequence: LAS1L NM_031206.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0650
• Publications: 0 publications found

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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant X-65534617-C-G is Benign according to our data. Variant chrX-65534617-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 464826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.065 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 2 Unknown,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031206.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAS1L	NM_031206.7	MANE Select	c.99G>C	p.Ser33Ser	synonymous	Exon 1 of 14	NP_112483.1	Q9Y4W2-1
	LAS1L	NM_001375328.1		c.99G>C	p.Ser33Ser	synonymous	Exon 1 of 14	NP_001362257.1
	LAS1L	NM_001170649.2		c.99G>C	p.Ser33Ser	synonymous	Exon 1 of 13	NP_001164120.1	Q9Y4W2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAS1L	ENST00000374811.8	TSL:1 MANE Select	c.99G>C	p.Ser33Ser	synonymous	Exon 1 of 14	ENSP00000363944.3	Q9Y4W2-1
	LAS1L	ENST00000374807.9	TSL:1	c.99G>C	p.Ser33Ser	synonymous	Exon 1 of 13	ENSP00000363940.5	Q9Y4W2-2
	LAS1L	ENST00000867035.1		c.99G>C	p.Ser33Ser	synonymous	Exon 1 of 14	ENSP00000537094.1

Frequencies

GnomAD3 genomes AF: 0.0000718 AC: 8 AN: 111402 Hom.: 0 Cov.: 23

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: 0.000151

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000106 AC: 17 AN: 159793 AF XY: 0.0000200

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: 0.000246

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000261 AC: 284 AN: 1087407 Hom.: 0 Cov.: 31 AF XY: 0.000194 AC XY: 69 AN XY: 355035

African (AFR) AF: 0.00 AC: 0 AN: 26170

American (AMR) AF: 0.00 AC: 0 AN: 34093

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19123

East Asian (EAS) AF: 0.00 AC: 0 AN: 29672

South Asian (SAS) AF: 0.00 AC: 0 AN: 52463

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39649

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4118

European-Non Finnish (NFE) AF: 0.000332 AC: 278 AN: 836433

Other (OTH) AF: 0.000131 AC: 6 AN: 45686

GnomAD4 genome AF: 0.0000718 AC: 8 AN: 111402 Hom.: 0 Cov.: 23 AF XY: 0.0000596 AC XY: 2 AN XY: 33574

African (AFR) AF: 0.00 AC: 0 AN: 30626

American (AMR) AF: 0.00 AC: 0 AN: 10499

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3533

South Asian (SAS) AF: 0.00 AC: 0 AN: 2630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6033

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.000151 AC: 8 AN: 53029

Other (OTH) AF: 0.00 AC: 0 AN: 1493

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000831

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Wilson-Turner syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.8
DANN	Benign	0.65
PhyloP100		0.065
PromoterAI		0.053	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs779407196; hg19: chrX-64754497;