X-37572300-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001170331.2(LANCL3):​c.430G>A​(p.Val144Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 112,260 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V144L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: LANCL3 NM_001170331.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14703977).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LANCL3	NM_001170331.2	c.430G>A	p.Val144Met	missense_variant	Exon 1 of 5	ENST00000378619.4	NP_001163802.1
LANCL3	NM_198511.3	c.430G>A	p.Val144Met	missense_variant	Exon 1 of 6		NP_940913.1
LANCL3	XM_011543904.3	c.-541G>A		upstream_gene_variant			XP_011542206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LANCL3	ENST00000378619.4	c.430G>A	p.Val144Met	missense_variant	Exon 1 of 5	1	NM_001170331.2	ENSP00000367882.4
LANCL3	ENST00000378621.7	c.430G>A	p.Val144Met	missense_variant	Exon 1 of 6	1		ENSP00000367885.3
ENSG00000250349	ENST00000465127.1	c.171+146300G>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1
LANCL3	ENST00000614025.4	c.430G>A	p.Val144Met	missense_variant	Exon 1 of 5	2		ENSP00000479231.1

Frequencies

GnomAD3 genomes AF: 0.0000267 AC: 3 AN: 112204 Hom.: 0 Cov.: 23 AF XY: 0.0000582 AC XY: 2 AN XY: 34370

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000569

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1045080 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 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: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000267 AC: 3 AN: 112260 Hom.: 0 Cov.: 23 AF XY: 0.0000581 AC XY: 2 AN XY: 34436

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000570

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	.;.;T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T;.;T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L;L
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.52	.;N;N
REVEL	Benign	0.081
Sift	Benign	0.13	.;T;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.15	B;B;B
Vest4		0.17
MutPred		0.42		Loss of ubiquitination at K149 (P = 0.0596);Loss of ubiquitination at K149 (P = 0.0596);Loss of ubiquitination at K149 (P = 0.0596);
MVP		0.35
MPC		0.53
ClinPred		0.48	T
GERP RS		4.1
Varity_R		0.075
gMVP		0.34

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; COSMIC: COSV66127767;