X-37572205-C-G

Variant names:

• chrX-37572205-C-G
• rs782551297
• NM_001170331.2:c.335C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001170331.2(LANCL3):​c.335C>G​(p.Pro112Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,162,157 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P112A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.0000019 (0 hom. 1 hem.)
• Consequence: LANCL3 NM_001170331.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04710132).

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.335C>G	p.Pro112Arg	missense	Exon 1 of 5	NP_001163802.1	Q6ZV70-1
	LANCL3	NM_198511.3		c.335C>G	p.Pro112Arg	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.335C>G	p.Pro112Arg	missense	Exon 1 of 5	ENSP00000367882.4	Q6ZV70-1
	LANCL3	ENST00000378621.7	TSL:1	c.335C>G	p.Pro112Arg	missense	Exon 1 of 6	ENSP00000367885.3	Q6ZV70-2
	ENSG00000250349	ENST00000465127.1	TSL:5	c.171+146205C>G		intron	N/A	ENSP00000417050.1	B4E171

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112110 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000899 AC: 1 AN: 111227 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000214

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000190 AC: 2 AN: 1050047 Hom.: 0 Cov.: 30 AF XY: 0.00000299 AC XY: 1 AN XY: 334741

African (AFR) AF: 0.00 AC: 0 AN: 25319

American (AMR) AF: 0.00 AC: 0 AN: 31383

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17991

East Asian (EAS) AF: 0.00 AC: 0 AN: 28865

South Asian (SAS) AF: 0.00 AC: 0 AN: 49080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2800

European-Non Finnish (NFE) AF: 0.00000243 AC: 2 AN: 822568

Other (OTH) AF: 0.00 AC: 0 AN: 44197

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112110 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34272

African (AFR) AF: 0.00 AC: 0 AN: 30894

American (AMR) AF: 0.00 AC: 0 AN: 10800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3516

South Asian (SAS) AF: 0.00 AC: 0 AN: 2693

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6135

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52999

Other (OTH) AF: 0.00 AC: 0 AN: 1517

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000896 AC: 1

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	0.10
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	18
DANN	Benign	0.86
DEOGEN2	Benign	0.0045	T
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.2
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.73	N
REVEL	Benign	0.014
Sift	Benign	0.61	T
Sift4G	Benign	0.65	T
Polyphen		0.0060	B
Vest4		0.072
MutPred		0.43		Loss of catalytic residue at P112 (P = 0.05)
MVP		0.093
MPC		0.51
ClinPred		0.027	T
GERP RS		2.8
Varity_R		0.087
gMVP		0.27
Mutation Taster		=94/6	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: rs782551297; hg19: chrX-37431458;