chrX-37572034-C-A

Variant names:

• chrX-37572034-C-A
• NM_001170331.2:c.164C>A

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.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. 13/20 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
• 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=0.118323445).

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.164C>A	p.Thr55Lys	missense	Exon 1 of 5	NP_001163802.1	Q6ZV70-1
	LANCL3	NM_198511.3		c.164C>A	p.Thr55Lys	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.164C>A	p.Thr55Lys	missense	Exon 1 of 5	ENSP00000367882.4	Q6ZV70-1
	LANCL3	ENST00000378621.7	TSL:1	c.164C>A	p.Thr55Lys	missense	Exon 1 of 6	ENSP00000367885.3	Q6ZV70-2
	ENSG00000250349	ENST00000465127.1	TSL:5	c.171+146034C>A		intron	N/A	ENSP00000417050.1	B4E171

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

African (AFR) AF: 0.00 AC: 0 AN: 25779

American (AMR) AF: 0.00 AC: 0 AN: 31768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18823

East Asian (EAS) AF: 0.00 AC: 0 AN: 28983

South Asian (SAS) AF: 0.00 AC: 0 AN: 51374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3206

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 827854

Other (OTH) AF: 0.00 AC: 0 AN: 44858

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.8
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.065
Sift	Benign	0.77	T
Sift4G	Benign	0.56	T
Polyphen		0.019	B
Vest4		0.11
MutPred		0.29		Gain of ubiquitination at T55 (P = 0.0069)
MVP		0.12
MPC		0.58
ClinPred		0.37	T
GERP RS		4.6
PromoterAI		0.0061	Neutral
Varity_R		0.14
gMVP		0.30
Mutation Taster		=85/15	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

hg19: chrX-37431287;