Variant X-37572270-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001170331.2(LANCL3):c.400G>A(p.Val134Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 112,050 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000058 ( 0 hom. 4 hem. )

Failed GnomAD Quality Control

Consequence

LANCL3
NM_001170331.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.89

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07948145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LANCL3	NM_001170331.2 linkuse as main transcript	c.400G>A	p.Val134Ile	missense_variant	1/5	ENST00000378619.4
LANCL3	NM_198511.3 linkuse as main transcript	c.400G>A	p.Val134Ile	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LANCL3	ENST00000378619.4 linkuse as main transcript	c.400G>A	p.Val134Ile	missense_variant	1/5	1	NM_001170331.2	P1	Q6ZV70-1
LANCL3	ENST00000378621.7 linkuse as main transcript	c.400G>A	p.Val134Ile	missense_variant	1/6	1			Q6ZV70-2
LANCL3	ENST00000614025.4 linkuse as main transcript	c.400G>A	p.Val134Ile	missense_variant	1/5	2			Q6ZV70-2

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34232

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:

0.000571

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

GnomAD3 exomes

AF:

0.0000308

AC:

AN:

97528

Hom.:

AF XY:

0.0000581

AC XY:

AN XY:

34446

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000379

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000577

AC:

AN:

1040699

Hom.:

Cov.:

AF XY:

0.0000118

AC XY:

AN XY:

337895

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000147

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000245

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34232

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000571

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000356

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.400G>A (p.V134I) alteration is located in exon 1 (coding exon 1) of the LANCL3 gene. This alteration results from a G to A substitution at nucleotide position 400, causing the valine (V) at amino acid position 134 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0075

.;.;T

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.75

T;.;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.079

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.015

N;N;N

MutationTaster

Benign

0.61

D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.16

.;N;N

REVEL

Benign

0.069

Sift

Benign

1.0

.;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.18

B;B;B

Vest4

0.037

MutPred

0.58

Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);

MVP

0.093

MPC

0.41

ClinPred

0.039

GERP RS

4.1

Varity_R

0.037

gMVP

0.093

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over