X-37655727-A-G

Variant names:

• chrX-37655727-A-G
• rs144498482
• NM_001170331.2:c.613A>G

Variant summary

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

The NM_001170331.2(LANCL3):​c.613A>G​(p.Ile205Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,091,770 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000046 (0 hom. 16 hem.)
• Consequence: LANCL3 NM_001170331.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.60

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=0.24028042).
• BS2: High Hemizygotes in GnomAdExome4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LANCL3	NM_001170331.2	c.613A>G	p.Ile205Val	missense_variant	Exon 2 of 5	ENST00000378619.4	NP_001163802.1
LANCL3	NM_198511.3	c.613A>G	p.Ile205Val	missense_variant	Exon 2 of 6		NP_940913.1
LANCL3	XM_011543904.3	c.67A>G	p.Ile23Val	missense_variant	Exon 2 of 5		XP_011542206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LANCL3	ENST00000378619.4	c.613A>G	p.Ile205Val	missense_variant	Exon 2 of 5	1	NM_001170331.2	ENSP00000367882.4
LANCL3	ENST00000378621.7	c.613A>G	p.Ile205Val	missense_variant	Exon 2 of 6	1		ENSP00000367885.3
ENSG00000250349	ENST00000465127.1	c.171+229727A>G		intron_variant	Intron 3 of 8	5		ENSP00000417050.1
LANCL3	ENST00000614025.4	c.613A>G	p.Ile205Val	missense_variant	Exon 2 of 5	2		ENSP00000479231.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.0000332 AC: 6 AN: 180651 Hom.: 0 AF XY: 0.0000153 AC XY: 1 AN XY: 65387

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000372

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000538

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000495

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000458 AC: 50 AN: 1091770 Hom.: 0 Cov.: 27 AF XY: 0.0000448 AC XY: 16 AN XY: 357406

Gnomad4 AFR exome AF: 0.000267

Gnomad4 AMR exome AF: 0.0000286

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000478

Gnomad4 OTH exome AF: 0.0000218

GnomAD4 genome Cov.: 23

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000412 AC: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.613A>G (p.I205V) alteration is located in exon 2 (coding exon 2) of the LANCL3 gene. This alteration results from a A to G substitution at nucleotide position 613, causing the isoleucine (I) at amino acid position 205 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	.;.;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T;.;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.98	L;L;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.45	.;N;N
REVEL	Benign	0.15
Sift	Benign	0.18	.;T;T
Sift4G	Benign	0.40	T;T;T
Polyphen		0.049	B;B;B
Vest4		0.39
MVP		0.61
MPC		0.42
ClinPred		0.12	T
GERP RS		5.0
Varity_R		0.17
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: rs144498482; hg19: chrX-37514980;