Variant 3-157028269-A-C 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_001004316.3(LEKR1):c.1535A>C(p.Lys512Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

LEKR1
NM_001004316.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.96

Variant links:

Genes affected

LEKR1 (HGNC:33765): (leucine, glutamate and lysine rich 1)

LEKR1 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=0.11524525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEKR1	NM_001004316.3 linkuse as main transcript	c.1535A>C	p.Lys512Thr	missense_variant	12/13	ENST00000356539.9	NP_001004316.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEKR1	ENST00000356539.9 linkuse as main transcript	c.1535A>C	p.Lys512Thr	missense_variant	12/13	5	NM_001004316.3	ENSP00000348936	P1
LEKR1	ENST00000470811.6 linkuse as main transcript	c.*1013A>C		3_prime_UTR_variant, NMD_transcript_variant	13/14	2		ENSP00000418214

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000320

AC:

AN:

250094

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135352

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000436

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:

0.00000479

AC:

AN:

1461342

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

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

Oct 03, 2023

The c.1535A>C (p.K512T) alteration is located in exon 12 (coding exon 11) of the LEKR1 gene. This alteration results from a A to C substitution at nucleotide position 1535, causing the lysine (K) at amino acid position 512 to be replaced by a threonine (T). 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

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0099

T;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.11

Sift

Benign

0.097

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.93

P;.

Vest4

0.23

MutPred

0.13

Loss of ubiquitination at K208 (P = 0.0019);.;

MVP

0.23

ClinPred

0.36

GERP RS

4.1

Varity_R

0.12

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