Variant X-37572042-G-C 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.172G>C(p.Ala58Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,178,767 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 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., 3 hem., cov: 23)

Exomes 𝑓: 0.000034 ( 0 hom. 10 hem. )

Consequence

LANCL3
NM_001170331.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.598

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=0.046595633).

BS2

High Hemizygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LANCL3	NM_001170331.2 linkuse as main transcript	c.172G>C	p.Ala58Pro	missense_variant	1/5	ENST00000378619.4
LANCL3	NM_198511.3 linkuse as main transcript	c.172G>C	p.Ala58Pro	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LANCL3	ENST00000378619.4 linkuse as main transcript	c.172G>C	p.Ala58Pro	missense_variant	1/5	1	NM_001170331.2	P1	Q6ZV70-1
LANCL3	ENST00000378621.7 linkuse as main transcript	c.172G>C	p.Ala58Pro	missense_variant	1/6	1			Q6ZV70-2
LANCL3	ENST00000614025.4 linkuse as main transcript	c.172G>C	p.Ala58Pro	missense_variant	1/5	2			Q6ZV70-2

Frequencies

GnomAD3 genomes

AF:

0.0000710

AC:

AN:

112727

Hom.:

Cov.:

AF XY:

0.0000859

AC XY:

AN XY:

34909

show subpopulations

Gnomad AFR

AF:

0.000161

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:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000326

AC:

AN:

122614

Hom.:

AF XY:

0.0000276

AC XY:

AN XY:

36276

show subpopulations

Gnomad AFR exome

AF:

0.000536

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000338

AC:

AN:

1066040

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

343370

show subpopulations

Gnomad4 AFR exome

AF:

0.000155

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:

0.0000350

Gnomad4 OTH exome

AF:

0.0000446

GnomAD4 genome

AF:

0.0000710

AC:

AN:

112727

Hom.:

Cov.:

AF XY:

0.0000859

AC XY:

AN XY:

34909

show subpopulations

Gnomad4 AFR

AF:

0.000161

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:

0.0000564

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000526

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 09, 2022

The c.172G>C (p.A58P) alteration is located in exon 1 (coding exon 1) of the LANCL3 gene. This alteration results from a G to C substitution at nucleotide position 172, causing the alanine (A) at amino acid position 58 to be replaced by a proline (P). 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

0.066

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.75

Cadd

Benign

9.1

Dann

Benign

0.72

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.55

T;.;T

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.047

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

N;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.78

Sift4G

Benign

0.37

T;T;T

Polyphen

0.077

B;B;B

Vest4

0.074

MutPred

0.35

Gain of disorder (P = 0.0828);Gain of disorder (P = 0.0828);Gain of disorder (P = 0.0828);

MVP

0.093

MPC

0.61

ClinPred

0.0072

GERP RS

2.3

Varity_R

0.064

gMVP

0.22

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