X-37572212-C-T

Variant summary

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

The NM_001170331.2(LANCL3):c.342C>T(p.Ala114=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,157,206 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 72 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 0.000080 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.00018 (0 hom. 69 hem.)
• Consequence: LANCL3 NM_001170331.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.508

Genes affected

LANCL3 (HGNC:24767): (LanC like family member 3) Predicted to be involved in carbohydrate metabolic process. Predicted to be active in plasma membrane. [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=-0.71).
• BP6: Variant X-37572212-C-T is Benign according to our data. Variant chrX-37572212-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660280.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.508 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LANCL3	NM_001170331.2	c.342C>T	p.Ala114=	synonymous_variant	1/5	ENST00000378619.4
LANCL3	NM_198511.3	c.342C>T	p.Ala114=	synonymous_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LANCL3	ENST00000378619.4	c.342C>T	p.Ala114=	synonymous_variant	1/5	1	NM_001170331.2	P1
LANCL3	ENST00000378621.7	c.342C>T	p.Ala114=	synonymous_variant	1/6	1
LANCL3	ENST00000614025.4	c.342C>T	p.Ala114=	synonymous_variant	1/5	2

Frequencies

GnomAD3 genomes AF: 0.0000803 AC: 9 AN: 112069 Hom.: 0 Cov.: 23 AF XY: 0.0000876 AC XY: 3 AN XY: 34237

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000185

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: 0.000113

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000861 AC: 9 AN: 104469 Hom.: 0 AF XY: 0.000151 AC XY: 4 AN XY: 26431

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000142

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: 0.000116

Gnomad OTH exome AF: 0.000338

GnomAD4 exome AF: 0.000180 AC: 188 AN: 1045087 Hom.: 0 Cov.: 29 AF XY: 0.000207 AC XY: 69 AN XY: 332621

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000228

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: 0.000216

Gnomad4 OTH exome AF: 0.0000909

GnomAD4 genome AF: 0.0000803 AC: 9 AN: 112119 Hom.: 0 Cov.: 23 AF XY: 0.0000875 AC XY: 3 AN XY: 34297

Gnomad4 AFR AF: 0.0000323

Gnomad4 AMR AF: 0.000185

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000113

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000285 Hom.: 2

Bravo AF: 0.000110

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

LANCL3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	10
Dann	Benign	0.94

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: rs181309411; hg19: chrX-37431465;