X-37572300-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001170331.2(LANCL3):​c.430G>C​(p.Val144Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000191 in 1,045,081 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000019 (0 hom. 0 hem.)
• Consequence: LANCL3 NM_001170331.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.54
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1516276).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170331.2. 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
	LANCL3	NM_001170331.2	MANE Select	c.430G>C	p.Val144Leu	missense	Exon 1 of 5	NP_001163802.1	Q6ZV70-1
	LANCL3	NM_198511.3		c.430G>C	p.Val144Leu	missense	Exon 1 of 6	NP_940913.1	Q6ZV70-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LANCL3	ENST00000378619.4	TSL:1 MANE Select	c.430G>C	p.Val144Leu	missense	Exon 1 of 5	ENSP00000367882.4	Q6ZV70-1
	LANCL3	ENST00000378621.7	TSL:1	c.430G>C	p.Val144Leu	missense	Exon 1 of 6	ENSP00000367885.3	Q6ZV70-2
	ENSG00000250349	ENST00000465127.1	TSL:5	c.171+146300G>C		intron	N/A	ENSP00000417050.1	B4E171

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000191 AC: 2 AN: 1045081 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 339921

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24861

American (AMR) AF: 0.00 AC: 0 AN: 27927

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18597

East Asian (EAS) AF: 0.00 AC: 0 AN: 27138

South Asian (SAS) AF: 0.00 AC: 0 AN: 49808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31929

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3350

European-Non Finnish (NFE) AF: 0.00000245 AC: 2 AN: 817327

Other (OTH) AF: 0.00 AC: 0 AN: 44144

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.25	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
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.5
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.092
Sift	Benign	0.39	T
Sift4G	Benign	0.61	T
Polyphen		0.16	B
Vest4		0.25
MutPred		0.44		Loss of methylation at K149 (P = 0.0791)
MVP		0.37
MPC		0.56
ClinPred		0.43	T
GERP RS		4.1
Varity_R		0.085
gMVP		0.37
Mutation Taster		=83/17	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: rs1458483436; hg19: chrX-37431553;