X-37572001-C-A

Position:

• chrX-37572001-C-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.131C>A​(p.Pro44Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,075,003 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000056 (0 hom. 2 hem.)
• Consequence: LANCL3 NM_001170331.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.25

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1791183).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LANCL3	NM_001170331.2	c.131C>A	p.Pro44Gln	missense_variant	1/5	ENST00000378619.4
LANCL3	NM_198511.3	c.131C>A	p.Pro44Gln	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LANCL3	ENST00000378619.4	c.131C>A	p.Pro44Gln	missense_variant	1/5	1	NM_001170331.2	P1
LANCL3	ENST00000378621.7	c.131C>A	p.Pro44Gln	missense_variant	1/6	1
LANCL3	ENST00000614025.4	c.131C>A	p.Pro44Gln	missense_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000558 AC: 6 AN: 1075003 Hom.: 0 Cov.: 29 AF XY: 0.00000576 AC XY: 2 AN XY: 347335

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: 0.00000602

Gnomad4 OTH exome AF: 0.0000222

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.131C>A (p.P44Q) alteration is located in exon 1 (coding exon 1) of the LANCL3 gene. This alteration results from a C to A substitution at nucleotide position 131, causing the proline (P) at amino acid position 44 to be replaced by a glutamine (Q). 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	0.082
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.055	.;.;T
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.60	T;.;T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N
MutationTaster	Benign	0.86	D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.1	.;N;N
REVEL	Benign	0.049
Sift	Benign	0.037	.;D;T
Sift4G	Benign	0.10	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.16
MutPred		0.31		Loss of glycosylation at P44 (P = 0.0469);Loss of glycosylation at P44 (P = 0.0469);Loss of glycosylation at P44 (P = 0.0469);
MVP		0.19
MPC		0.44
ClinPred		0.22	T
GERP RS		3.9
Varity_R		0.080
gMVP		0.18

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: rs1487020854; hg19: chrX-37431254;