X-37572300-G-T

Variant names:

• chrX-37572300-G-T
• rs1458483436
• NM_001170331.2:c.430G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001170331.2(LANCL3):​c.430G>T​(p.Val144Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000478 in 1,045,080 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000048 (0 hom. 1 hem.)
• Consequence: LANCL3 NM_001170331.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.54

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]

ENSG00000250349 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13217339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LANCL3	NM_001170331.2	c.430G>T	p.Val144Leu	missense_variant	Exon 1 of 5	ENST00000378619.4	NP_001163802.1
LANCL3	NM_198511.3	c.430G>T	p.Val144Leu	missense_variant	Exon 1 of 6		NP_940913.1
LANCL3	XM_011543904.3	c.-541G>T		upstream_gene_variant			XP_011542206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LANCL3	ENST00000378619.4	c.430G>T	p.Val144Leu	missense_variant	Exon 1 of 5	1	NM_001170331.2	ENSP00000367882.4
LANCL3	ENST00000378621.7	c.430G>T	p.Val144Leu	missense_variant	Exon 1 of 6	1		ENSP00000367885.3
ENSG00000250349	ENST00000465127.1	c.171+146300G>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1
LANCL3	ENST00000614025.4	c.430G>T	p.Val144Leu	missense_variant	Exon 1 of 5	2		ENSP00000479231.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.0000197 AC: 2 AN: 101418 Hom.: 0 AF XY: 0.0000274 AC XY: 1 AN XY: 36504

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000253

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000478 AC: 5 AN: 1045080 Hom.: 0 Cov.: 29 AF XY: 0.00000294 AC XY: 1 AN XY: 339920

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000737

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000367

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.430G>T (p.V144L) alteration is located in exon 1 (coding exon 1) of the LANCL3 gene. This alteration results from a G to T substitution at nucleotide position 430, causing the valine (V) at amino acid position 144 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	.;.;T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.63	T;.;T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L;L
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.67	.;N;N
REVEL	Benign	0.092
Sift	Benign	0.39	.;T;T
Sift4G	Benign	0.61	T;T;T
Polyphen		0.16	B;B;B
Vest4		0.25
MutPred		0.44		Loss of methylation at K149 (P = 0.0791);Loss of methylation at K149 (P = 0.0791);Loss of methylation at K149 (P = 0.0791);
MVP		0.36
MPC		0.56
ClinPred		0.15	T
GERP RS		4.1
Varity_R		0.085
gMVP		0.37

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: rs1458483436; hg19: chrX-37431553;