Genetic Variant LANCL3:p.His136Gln (chrX-37572278-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001170331.2(LANCL3):c.408C>G(p.His136Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000078 in 1,153,266 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.0000067 ( 0 hom. 0 hem. )

Consequence

LANCL3
NM_001170331.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.188

Publications

0 publications found

Variant links:

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]

LANCL3 links:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.123153776).

BS2

High Hemizygotes in GnomAd4 at 2 gene

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.408C>G	p.His136Gln	missense	Exon 1 of 5	NP_001163802.1	Q6ZV70-1
	LANCL3	NM_198511.3		c.408C>G	p.His136Gln	missense	Exon 1 of 6	NP_940913.1	Q6ZV70-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LANCL3	ENST00000378619.4	TSL:1 MANE Select	c.408C>G	p.His136Gln	missense	Exon 1 of 5	ENSP00000367882.4	Q6ZV70-1
LANCL3	ENST00000378621.7	TSL:1	c.408C>G	p.His136Gln	missense	Exon 1 of 6	ENSP00000367885.3	Q6ZV70-2
ENSG00000250349	ENST00000465127.1	TSL:5	c.171+146278C>G		intron	N/A	ENSP00000417050.1	B4E171

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112105

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000185

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:

0.0000713

AC:

AN:

98205

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000363

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

AF:

0.00000672

AC:

AN:

1041161

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

338305

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24841

American (AMR)

AF:

0.000250

AC:

AN:

27976

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18562

East Asian (EAS)

AF:

0.00

AC:

AN:

27146

South Asian (SAS)

AF:

0.00

AC:

AN:

49735

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29168

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2964

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

816651

Other (OTH)

AF:

0.00

AC:

AN:

44118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112105

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34259

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30898

American (AMR)

AF:

0.000185

AC:

AN:

10783

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3497

South Asian (SAS)

AF:

0.00

AC:

AN:

2683

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6152

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53007

Other (OTH)

AF:

0.00

AC:

AN:

1521

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.031

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.67

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

0.19

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.8

REVEL

Benign

0.068

Sift

Benign

0.40

Sift4G

Benign

0.42

Polyphen

0.79

Vest4

0.081

MutPred

0.64

Gain of catalytic residue at H136 (P = 0.2991)

MVP

0.28

MPC

0.49

ClinPred

0.050

GERP RS

4.1

Varity_R

0.28

gMVP

0.17

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over