X-37572138-G-A

Variant names:

• chrX-37572138-G-A
• rs1173589643
• NM_001170331.2:c.268G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001170331.2(LANCL3):​c.268G>A​(p.Glu90Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000925 in 1,081,349 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. 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. E90Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: LANCL3 NM_001170331.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.29
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31828964).

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.268G>A	p.Glu90Lys	missense	Exon 1 of 5	NP_001163802.1	Q6ZV70-1
	LANCL3	NM_198511.3		c.268G>A	p.Glu90Lys	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.268G>A	p.Glu90Lys	missense	Exon 1 of 5	ENSP00000367882.4	Q6ZV70-1
	LANCL3	ENST00000378621.7	TSL:1	c.268G>A	p.Glu90Lys	missense	Exon 1 of 6	ENSP00000367885.3	Q6ZV70-2
	ENSG00000250349	ENST00000465127.1	TSL:5	c.171+146138G>A		intron	N/A	ENSP00000417050.1	B4E171

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.25e-7 AC: 1 AN: 1081349 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 355673

African (AFR) AF: 0.00 AC: 0 AN: 26173

American (AMR) AF: 0.00 AC: 0 AN: 34900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19201

East Asian (EAS) AF: 0.00 AC: 0 AN: 30043

South Asian (SAS) AF: 0.00 AC: 0 AN: 53363

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29995

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2900

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 839205

Other (OTH) AF: 0.00 AC: 0 AN: 45569

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		8.3
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.18
Sift	Benign	0.75	T
Sift4G	Benign	0.74	T
Polyphen		0.56	P
Vest4		0.24
MutPred		0.68		Gain of MoRF binding (P = 0.0099)
MVP		0.24
MPC		0.68
ClinPred		0.61	D
GERP RS		3.8
PromoterAI		0.22	Neutral
Varity_R		0.24
gMVP		0.28
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1173589643; hg19: chrX-37431391;