X-37572034-C-A

Position:

• chrX-37572034-C-A

Variant summary

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

The NM_001170331.2(LANCL3):​c.164C>A​(p.Thr55Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: LANCL3 NM_001170331.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.78

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 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=0.118323445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LANCL3	NM_001170331.2	c.164C>A	p.Thr55Lys	missense_variant	1/5	ENST00000378619.4
LANCL3	NM_198511.3	c.164C>A	p.Thr55Lys	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LANCL3	ENST00000378619.4	c.164C>A	p.Thr55Lys	missense_variant	1/5	1	NM_001170331.2	P1
LANCL3	ENST00000378621.7	c.164C>A	p.Thr55Lys	missense_variant	1/6	1
LANCL3	ENST00000614025.4	c.164C>A	p.Thr55Lys	missense_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1067505 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 343875

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 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

May 13, 2024

The c.164C>A (p.T55K) 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 164, causing the threonine (T) at amino acid position 55 to be replaced by a lysine (K). 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	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.0080	.;.;T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.56	T;.;T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;N
MutationTaster	Benign	0.79	D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.48	.;N;N
REVEL	Benign	0.065
Sift	Benign	0.77	.;T;T
Sift4G	Benign	0.56	T;T;T
Polyphen		0.019	B;B;B
Vest4		0.11
MutPred		0.29		Gain of ubiquitination at T55 (P = 0.0069);Gain of ubiquitination at T55 (P = 0.0069);Gain of ubiquitination at T55 (P = 0.0069);
MVP		0.12
MPC		0.58
ClinPred		0.37	T
GERP RS		4.6
Varity_R		0.14
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-37431287;