dbSNP rs1458483436: LANCL3:p.Val144Met (chrX-37572300-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14703977).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LANCL3	NM_001170331.2 link	c.430G>A	p.Val144Met	missense_variant	Exon 1 of 5	ENST00000378619.4	NP_001163802.1	Q6ZV70-1
LANCL3	NM_198511.3 link	c.430G>A	p.Val144Met	missense_variant	Exon 1 of 6		NP_940913.1	Q6ZV70-2
LANCL3	XM_011543904.3 link	c.-541G>A		upstream_gene_variant			XP_011542206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LANCL3	ENST00000378619.4 link	c.430G>A	p.Val144Met	missense_variant	Exon 1 of 5	1	NM_001170331.2	ENSP00000367882.4	Q6ZV70-1
LANCL3	ENST00000378621.7 link	c.430G>A	p.Val144Met	missense_variant	Exon 1 of 6	1		ENSP00000367885.3	Q6ZV70-2
ENSG00000250349	ENST00000465127.1 link	c.171+146300G>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1	B4E171
LANCL3	ENST00000614025.4 link	c.430G>A	p.Val144Met	missense_variant	Exon 1 of 5	2		ENSP00000479231.1	Q6ZV70-2

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112204

Hom.:

Cov.:

AF XY:

0.0000582

AC XY:

AN XY:

34370

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112260

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34436

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000570

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;.;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.81

T;.;T

M_CAP

Benign

0.083

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L;L

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.52

.;N;N

REVEL

Benign

0.081

Sift

Benign

0.13

.;T;T

Sift4G

Benign

0.22

T;T;T

Polyphen

0.15

B;B;B

Vest4

0.17

MutPred

0.42

Loss of ubiquitination at K149 (P = 0.0596);Loss of ubiquitination at K149 (P = 0.0596);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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over