X-37572217-C-T

Position:

• chrX-37572217-C-T

Variant summary

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

The NM_001170331.2(LANCL3):​c.347C>T​(p.Thr116Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.6e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: LANCL3 NM_001170331.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25

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 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=0.15061632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LANCL3	NM_001170331.2	c.347C>T	p.Thr116Ile	missense_variant	1/5	ENST00000378619.4
LANCL3	NM_198511.3	c.347C>T	p.Thr116Ile	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LANCL3	ENST00000378619.4	c.347C>T	p.Thr116Ile	missense_variant	1/5	1	NM_001170331.2	P1
LANCL3	ENST00000378621.7	c.347C>T	p.Thr116Ile	missense_variant	1/6	1
LANCL3	ENST00000614025.4	c.347C>T	p.Thr116Ile	missense_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.59e-7 AC: 1 AN: 1042784 Hom.: 0 Cov.: 29 AF XY: 0.00000301 AC XY: 1 AN XY: 331728

Gnomad4 AFR exome AF: 0.0000399

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.: 24

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

Oct 27, 2022

The c.347C>T (p.T116I) alteration is located in exon 1 (coding exon 1) of the LANCL3 gene. This alteration results from a C to T substitution at nucleotide position 347, causing the threonine (T) at amino acid position 116 to be replaced by an isoleucine (I). 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	Uncertain	0.46
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	.;.;T
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.79	T;.;T
M_CAP	Pathogenic	0.58	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;L
MutationTaster	Benign	0.98	D;D
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-1.3	.;N;N
REVEL	Benign	0.056
Sift	Benign	0.28	.;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.032	B;B;B
Vest4		0.28
MutPred		0.43		Loss of glycosylation at T116 (P = 0.0231);Loss of glycosylation at T116 (P = 0.0231);Loss of glycosylation at T116 (P = 0.0231);
MVP		0.19
MPC		0.53
ClinPred		0.46	T
GERP RS		3.8
Varity_R		0.18
gMVP		0.31

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-37431470;