X-37572204-C-G

Variant names:

• chrX-37572204-C-G
• rs781851788
• NM_001170331.2:c.334C>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.334C>G​(p.Pro112Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 112,143 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. 14/21 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. P112R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.0000029 (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: 1.76
• 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=0.027060866).

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.334C>G	p.Pro112Ala	missense	Exon 1 of 5	NP_001163802.1	Q6ZV70-1
	LANCL3	NM_198511.3		c.334C>G	p.Pro112Ala	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.334C>G	p.Pro112Ala	missense	Exon 1 of 5	ENSP00000367882.4	Q6ZV70-1
	LANCL3	ENST00000378621.7	TSL:1	c.334C>G	p.Pro112Ala	missense	Exon 1 of 6	ENSP00000367885.3	Q6ZV70-2
	ENSG00000250349	ENST00000465127.1	TSL:5	c.171+146204C>G		intron	N/A	ENSP00000417050.1	B4E171

Frequencies

GnomAD3 genomes AF: 0.0000446 AC: 5 AN: 112143 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000162

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000176 AC: 2 AN: 113336 AF XY: 0.0000342

Gnomad AFR exome AF: 0.000266

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000285 AC: 3 AN: 1052049 Hom.: 0 Cov.: 30 AF XY: 0.00000298 AC XY: 1 AN XY: 335953

African (AFR) AF: 0.000118 AC: 3 AN: 25368

American (AMR) AF: 0.00 AC: 0 AN: 31697

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18027

East Asian (EAS) AF: 0.00 AC: 0 AN: 28967

South Asian (SAS) AF: 0.00 AC: 0 AN: 49257

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2807

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 823697

Other (OTH) AF: 0.00 AC: 0 AN: 44251

GnomAD4 genome AF: 0.0000446 AC: 5 AN: 112143 Hom.: 0 Cov.: 24 AF XY: 0.0000292 AC XY: 1 AN XY: 34299

African (AFR) AF: 0.000162 AC: 5 AN: 30898

American (AMR) AF: 0.00 AC: 0 AN: 10804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3521

South Asian (SAS) AF: 0.00 AC: 0 AN: 2689

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6138

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53011

Other (OTH) AF: 0.00 AC: 0 AN: 1520

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.00000892 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	0.056
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.0051	T
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.40	N
PhyloP100		1.8
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.14	N
REVEL	Benign	0.028
Sift	Benign	0.84	T
Sift4G	Benign	0.79	T
Polyphen		0.0	B
Vest4		0.075
MutPred		0.37		Loss of catalytic residue at P112 (P = 0.0225)
MVP		0.082
MPC		0.46
ClinPred		0.0066	T
GERP RS		2.7
Varity_R		0.034
gMVP		0.19
Mutation Taster		=90/10	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: rs781851788; hg19: chrX-37431457;