Variant chr3-156942645-A-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_001004316.3(LEKR1):c.676A>T(p.Ile226Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000268 in 1,119,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 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: 0.0000027 ( 0 hom. )

Consequence

LEKR1
NM_001004316.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61

Variant links:

Genes affected

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

LEKR1 links:

LEKR1 (HGNC:):

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=0.12490046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEKR1	NM_001004316.3 linkuse as main transcript	c.676A>T	p.Ile226Phe	missense_variant	6/13	ENST00000356539.9	NP_001004316.2	J3KP02

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LEKR1	ENST00000356539.9 linkuse as main transcript	c.676A>T	p.Ile226Phe	missense_variant	6/13	5	NM_001004316.3	ENSP00000348936.4	J3KP02
LEKR1	ENST00000470811.6 linkuse as main transcript	n.676A>T		non_coding_transcript_exon_variant	6/14	2		ENSP00000418214.2	A0A8I5FW65
LEKR1	ENST00000489350.5 linkuse as main transcript	n.377A>T		non_coding_transcript_exon_variant	4/5	3
LEKR1	ENST00000495252.1 linkuse as main transcript	n.321A>T		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

121076

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

65264

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000524

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:

0.000269

GnomAD4 exome

AF:

0.00000268

AC:

AN:

1119140

Hom.:

Cov.:

AF XY:

0.00000364

AC XY:

AN XY:

549058

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000435

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:

0.00000109

Gnomad4 OTH exome

AF:

0.0000245

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

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

Jun 11, 2024

The c.676A>T (p.I226F) alteration is located in exon 6 (coding exon 5) of the LEKR1 gene. This alteration results from a A to T substitution at nucleotide position 676, causing the isoleucine (I) at amino acid position 226 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

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.97

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.76

M_CAP

Benign

0.020

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.6

REVEL

Benign

0.062

Sift

Benign

0.031

Sift4G

Uncertain

0.044

Vest4

0.31

MutPred

0.27

Loss of catalytic residue at I226 (P = 0.0571);

MVP

0.29

ClinPred

0.24

GERP RS

5.4

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