X-37572138-G-C

Variant names:

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

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>C​(p.Glu90Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 112,459 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000013 (0 hom. 6 hem.)
  • Failed GnomAD Quality Control
• Consequence: LANCL3 NM_001170331.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.35157716).

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>C	p.Glu90Gln	missense	Exon 1 of 5	NP_001163802.1	Q6ZV70-1
	LANCL3	NM_198511.3		c.268G>C	p.Glu90Gln	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>C	p.Glu90Gln	missense	Exon 1 of 5	ENSP00000367882.4	Q6ZV70-1
	LANCL3	ENST00000378621.7	TSL:1	c.268G>C	p.Glu90Gln	missense	Exon 1 of 6	ENSP00000367885.3	Q6ZV70-2
	ENSG00000250349	ENST00000465127.1	TSL:5	c.171+146138G>C		intron	N/A	ENSP00000417050.1	B4E171

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112459 Hom.: 0 Cov.: 23

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: 0.0000377

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000653 AC: 1 AN: 153249 AF XY: 0.0000187

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: 0.0000148

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000129 AC: 14 AN: 1081351 Hom.: 0 Cov.: 30 AF XY: 0.0000169 AC XY: 6 AN XY: 355675

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: 0.0000155 AC: 13 AN: 839207

Other (OTH) AF: 0.0000219 AC: 1 AN: 45569

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112459 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34611

African (AFR) AF: 0.00 AC: 0 AN: 31011

American (AMR) AF: 0.00 AC: 0 AN: 10828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3536

South Asian (SAS) AF: 0.00 AC: 0 AN: 2739

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6179

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000377 AC: 2 AN: 53080

Other (OTH) AF: 0.00 AC: 0 AN: 1522

Alfa AF: 0.0000868 Hom.: 1

Bravo AF: 0.0000189

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	0.12
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		8.3
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.16
Sift	Benign	0.48	T
Sift4G	Benign	0.51	T
Polyphen		0.72	P
Vest4		0.13
MutPred		0.63		Gain of MoRF binding (P = 0.0352)
MVP		0.41
MPC		0.50
ClinPred		0.44	T
GERP RS		3.8
PromoterAI		0.014	Neutral
Varity_R		0.18
gMVP		0.22
Mutation Taster		=87/13	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: rs1173589643; hg19: chrX-37431391;