Variant X-37572039-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001170331.2(LANCL3):c.169G>A(p.Gly57Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000709 in 112,839 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000047 ( 0 hom. 16 hem. )

Failed GnomAD Quality Control

Consequence

LANCL3
NM_001170331.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.971

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.063085645).

BS2

High Hemizygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LANCL3	NM_001170331.2 linkuse as main transcript	c.169G>A	p.Gly57Arg	missense_variant	1/5	ENST00000378619.4
LANCL3	NM_198511.3 linkuse as main transcript	c.169G>A	p.Gly57Arg	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LANCL3	ENST00000378619.4 linkuse as main transcript	c.169G>A	p.Gly57Arg	missense_variant	1/5	1	NM_001170331.2	P1	Q6ZV70-1
LANCL3	ENST00000378621.7 linkuse as main transcript	c.169G>A	p.Gly57Arg	missense_variant	1/6	1			Q6ZV70-2
LANCL3	ENST00000614025.4 linkuse as main transcript	c.169G>A	p.Gly57Arg	missense_variant	1/5	2			Q6ZV70-2

Frequencies

GnomAD3 genomes

AF:

0.0000709

AC:

AN:

112839

Hom.:

Cov.:

AF XY:

0.0000571

AC XY:

AN XY:

35001

show subpopulations

Gnomad AFR

AF:

0.0000321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000807

AC:

AN:

123976

Hom.:

AF XY:

0.00

AC XY:

AN XY:

36632

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000468

AC:

AN:

1067272

Hom.:

Cov.:

AF XY:

0.0000465

AC XY:

AN XY:

344064

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000345

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000568

Gnomad4 OTH exome

AF:

0.0000446

GnomAD4 genome

AF:

0.0000709

AC:

AN:

112839

Hom.:

Cov.:

AF XY:

0.0000571

AC XY:

AN XY:

35001

show subpopulations

Gnomad4 AFR

AF:

0.0000321

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000176

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

Jan 04, 2024

The c.169G>A (p.G57R) 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 169, causing the glycine (G) at amino acid position 57 to be replaced by an arginine (R). 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

0.15

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.95

Cadd

Benign

7.6

Dann

Benign

0.86

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.60

T;.;T

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.063

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

N;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.80

Sift4G

Benign

0.34

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.053

MutPred

0.34

Gain of methylation at G57 (P = 0.0267);Gain of methylation at G57 (P = 0.0267);Gain of methylation at G57 (P = 0.0267);

MVP

0.043

MPC

0.56

ClinPred

0.024

GERP RS

2.1

Varity_R

0.045

gMVP

0.32

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