Variant X-37655754-A-G 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.640A>G(p.Ile214Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000782 in 1,202,423 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 32 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.000081 ( 0 hom. 28 hem. )

Consequence

LANCL3
NM_001170331.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98

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=0.04169923).

BS2

High Hemizygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LANCL3	NM_001170331.2 linkuse as main transcript	c.640A>G	p.Ile214Val	missense_variant	2/5	ENST00000378619.4
LANCL3	NM_198511.3 linkuse as main transcript	c.640A>G	p.Ile214Val	missense_variant	2/6
LANCL3	XM_011543904.3 linkuse as main transcript	c.94A>G	p.Ile32Val	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LANCL3	ENST00000378619.4 linkuse as main transcript	c.640A>G	p.Ile214Val	missense_variant	2/5	1	NM_001170331.2	P1	Q6ZV70-1
LANCL3	ENST00000378621.7 linkuse as main transcript	c.640A>G	p.Ile214Val	missense_variant	2/6	1			Q6ZV70-2
LANCL3	ENST00000614025.4 linkuse as main transcript	c.640A>G	p.Ile214Val	missense_variant	2/5	2			Q6ZV70-2

Frequencies

GnomAD3 genomes

AF:

0.0000537

AC:

AN:

111637

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33799

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000497

AC:

AN:

181244

Hom.:

AF XY:

0.0000607

AC XY:

AN XY:

65904

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:

0.000111

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000807

AC:

AN:

1090786

Hom.:

Cov.:

AF XY:

0.0000785

AC XY:

AN XY:

356480

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.0000436

GnomAD4 genome

AF:

0.0000537

AC:

AN:

111637

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33799

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000741

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

Apr 22, 2022

The c.640A>G (p.I214V) alteration is located in exon 2 (coding exon 2) of the LANCL3 gene. This alteration results from a A to G substitution at nucleotide position 640, causing the isoleucine (I) at amino acid position 214 to be replaced by a valine (V). 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

0.056

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.96

Cadd

Benign

9.6

Dann

Benign

0.83

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.68

T;.;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.042

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.90

N;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.37

Sift4G

Benign

0.32

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.048

MutPred

0.34

Gain of methylation at K215 (P = 0.0708);Gain of methylation at K215 (P = 0.0708);Gain of methylation at K215 (P = 0.0708);

MVP

0.082

MPC

0.39

ClinPred

0.034

GERP RS

-0.0092

Varity_R

0.039

gMVP

0.085

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