Genetic Variant NM_001170331.2:c.430G>A (chrX-37572300-G-A) – 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.430G>A(p.Val144Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 112,260 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V144L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

LANCL3
NM_001170331.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.54

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=0.14703977).

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.430G>A	p.Val144Met	missense	Exon 1 of 5	NP_001163802.1	Q6ZV70-1
	LANCL3	NM_198511.3		c.430G>A	p.Val144Met	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.430G>A	p.Val144Met	missense	Exon 1 of 5	ENSP00000367882.4	Q6ZV70-1
LANCL3	ENST00000378621.7	TSL:1	c.430G>A	p.Val144Met	missense	Exon 1 of 6	ENSP00000367885.3	Q6ZV70-2
ENSG00000250349	ENST00000465127.1	TSL:5	c.171+146300G>A		intron	N/A	ENSP00000417050.1	B4E171

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000569

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1045080

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

339920

African (AFR)

AF:

0.00

AC:

AN:

24861

American (AMR)

AF:

0.00

AC:

AN:

27927

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18597

East Asian (EAS)

AF:

0.00

AC:

AN:

27138

South Asian (SAS)

AF:

0.00

AC:

AN:

49808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31929

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3350

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

817326

Other (OTH)

AF:

0.00

AC:

AN:

44144

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112260

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34436

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31002

American (AMR)

AF:

0.00

AC:

AN:

10789

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.000570

AC:

AN:

3507

South Asian (SAS)

AF:

0.00

AC:

AN:

2683

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6149

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53051

Other (OTH)

AF:

0.00

AC:

AN:

1531

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.81

M_CAP

Benign

0.083

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

5.5

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.52

REVEL

Benign

0.081

Sift

Benign

0.13

Sift4G

Benign

0.22

Polyphen

0.15

Vest4

0.17

MutPred

0.42

Loss of ubiquitination at K149 (P = 0.0596)

MVP

0.35

MPC

0.53

ClinPred

0.48

GERP RS

4.1

Varity_R

0.075

gMVP

0.34

Mutation Taster

=87/13

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over