X-37572324-G-T

Variant names:

• chrX-37572324-G-T
• rs781795045
• NM_001170331.2:c.454G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001170331.2(LANCL3):​c.454G>T​(p.Ala152Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000953 in 1,049,211 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. A152V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.5e-7 (0 hom. 0 hem.)
• Consequence: LANCL3 NM_001170331.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.18
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09815934).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170331.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LANCL3	NM_001170331.2	MANE Select	c.454G>T	p.Ala152Ser	missense	Exon 1 of 5	NP_001163802.1	Q6ZV70-1
	LANCL3	NM_198511.3		c.454G>T	p.Ala152Ser	missense	Exon 1 of 6	NP_940913.1	Q6ZV70-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LANCL3	ENST00000378619.4	TSL:1 MANE Select	c.454G>T	p.Ala152Ser	missense	Exon 1 of 5	ENSP00000367882.4	Q6ZV70-1
	LANCL3	ENST00000378621.7	TSL:1	c.454G>T	p.Ala152Ser	missense	Exon 1 of 6	ENSP00000367885.3	Q6ZV70-2
	ENSG00000250349	ENST00000465127.1	TSL:5	c.171+146324G>T		intron	N/A	ENSP00000417050.1	B4E171

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.53e-7 AC: 1 AN: 1049211 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 341917

African (AFR) AF: 0.0000402 AC: 1 AN: 24896

American (AMR) AF: 0.00 AC: 0 AN: 27944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18616

East Asian (EAS) AF: 0.00 AC: 0 AN: 27160

South Asian (SAS) AF: 0.00 AC: 0 AN: 49835

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3713

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 818416

Other (OTH) AF: 0.00 AC: 0 AN: 44259

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.0052	T
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		4.2
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.68	N
REVEL	Benign	0.078
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.056
MutPred		0.51		Loss of ubiquitination at K149 (P = 0.0896)
MVP		0.14
MPC		0.43
ClinPred		0.25	T
GERP RS		3.2
Varity_R		0.13
gMVP		0.077
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs781795045; hg19: chrX-37431577;