Variant 7-55366147-C-T 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_018697.4(LANCL2):c.122C>T(p.Ser41Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,398,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

LANCL2
NM_018697.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

Variant links:

Genes affected

LANCL2 (HGNC:6509): (LanC like glutathione S-transferase 2) Enables phosphatidylinositol-3-phosphate binding activity; phosphatidylinositol-4-phosphate binding activity; and phosphatidylinositol-5-phosphate binding activity. Involved in negative regulation of transcription, DNA-templated and positive regulation of abscisic acid-activated signaling pathway. Located in several cellular components, including cortical actin cytoskeleton; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LANCL2 links:

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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=0.124240726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LANCL2	NM_018697.4 linkuse as main transcript	c.122C>T	p.Ser41Phe	missense_variant	1/9	ENST00000254770.3	NP_061167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LANCL2	ENST00000254770.3 linkuse as main transcript	c.122C>T	p.Ser41Phe	missense_variant	1/9	1	NM_018697.4	ENSP00000254770	P1
LANCL2	ENST00000452107.6 linkuse as main transcript	c.38C>T	p.Ser13Phe	missense_variant, NMD_transcript_variant	1/10	5		ENSP00000387598

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000600

AC:

AN:

166628

Hom.:

AF XY:

0.00

AC XY:

AN XY:

90660

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:

0.0000143

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000429

AC:

AN:

1398782

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

689762

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:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000464

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 14, 2023

The c.122C>T (p.S41F) alteration is located in exon 1 (coding exon 1) of the LANCL2 gene. This alteration results from a C to T substitution at nucleotide position 122, causing the serine (S) at amino acid position 41 to be replaced by a phenylalanine (F). 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

0.14

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.026

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.30

M_CAP

Benign

0.0079

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.2

REVEL

Benign

0.049

Sift

Benign

0.052

Sift4G

Uncertain

0.024

Polyphen

0.070

Vest4

0.097

MutPred

0.43

Loss of glycosylation at S41 (P = 0.0011);

MVP

0.18

MPC

0.31

ClinPred

0.17

GERP RS

3.5

Varity_R

0.064

gMVP

0.28

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