Genetic Variant LANCL3:p.Ala152Thr (chrX-37572324-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001170331.2(LANCL3):c.454G>A(p.Ala152Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000253 in 1,161,514 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 79 hemizygotes 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A152V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., 32 hem., cov: 23)

Exomes 𝑓: 0.00016 ( 0 hom. 47 hem. )

Consequence

LANCL3
NM_001170331.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.18

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008877426).

BS2

High Hemizygotes in GnomAd4 at 32 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.454G>A	p.Ala152Thr	missense	Exon 1 of 5	NP_001163802.1	Q6ZV70-1
	LANCL3	NM_198511.3		c.454G>A	p.Ala152Thr	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.454G>A	p.Ala152Thr	missense	Exon 1 of 5	ENSP00000367882.4	Q6ZV70-1
LANCL3	ENST00000378621.7	TSL:1	c.454G>A	p.Ala152Thr	missense	Exon 1 of 6	ENSP00000367885.3	Q6ZV70-2
ENSG00000250349	ENST00000465127.1	TSL:5	c.171+146324G>A		intron	N/A	ENSP00000417050.1	B4E171

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

121

AN:

112246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00350

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000650

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.0000377

Gnomad OTH

AF:

0.00133

GnomAD2 exomes

AF:

0.000269

AC:

AN:

103991

AF XY:

0.000188

show subpopulations

Gnomad AFR exome

AF:

0.00357

Gnomad AMR exome

AF:

0.000155

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000128

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000165

AC:

173

AN:

1049214

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

341920

show subpopulations

African (AFR)

AF:

0.00478

AC:

119

AN:

24896

American (AMR)

AF:

0.000179

AC:

AN:

27944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18616

East Asian (EAS)

AF:

0.00

AC:

AN:

27160

South Asian (SAS)

AF:

0.0000201

AC:

AN:

49835

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34376

Middle Eastern (MID)

AF:

0.000539

AC:

AN:

3713

European-Non Finnish (NFE)

AF:

0.0000293

AC:

AN:

818415

Other (OTH)

AF:

0.000497

AC:

AN:

44259

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00108

AC:

121

AN:

112300

Hom.:

Cov.:

AF XY:

0.000929

AC XY:

AN XY:

34460

show subpopulations

African (AFR)

AF:

0.00349

AC:

108

AN:

30961

American (AMR)

AF:

0.000649

AC:

AN:

10790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3505

South Asian (SAS)

AF:

0.00

AC:

AN:

2687

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6172

Middle Eastern (MID)

AF:

0.00917

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000377

AC:

AN:

53109

Other (OTH)

AF:

0.00131

AC:

AN:

1527

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000781

Hom.:

Bravo

AF:

0.00125

ExAC

AF:

0.0000859

AC:

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

0.083

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.81

M_CAP

Benign

0.084

MetaRNN

Benign

0.0089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

4.2

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.36

REVEL

Benign

0.057

Sift

Benign

0.27

Sift4G

Benign

0.42

Polyphen

0.0040

Vest4

0.092

MVP

0.27

MPC

0.51

ClinPred

0.018

GERP RS

3.2

Varity_R

0.14

gMVP

0.079

Mutation Taster

=85/15

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over