3-157011489-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004316.3(LEKR1):​c.1186G>A​(p.Asp396Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,611,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

LEKR1
NM_001004316.3 missense

Scores

7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.84
Variant links:
Genes affected
LEKR1 (HGNC:33765): (leucine, glutamate and lysine rich 1)

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=0.12845483).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LEKR1NM_001004316.3 linkc.1186G>A p.Asp396Asn missense_variant Exon 10 of 13 ENST00000356539.9 NP_001004316.2 J3KP02

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LEKR1ENST00000356539.9 linkc.1186G>A p.Asp396Asn missense_variant Exon 10 of 13 5 NM_001004316.3 ENSP00000348936.4 J3KP02
LEKR1ENST00000470811.6 linkn.*664G>A non_coding_transcript_exon_variant Exon 11 of 14 2 ENSP00000418214.2 A0A8I5FW65
LEKR1ENST00000470811.6 linkn.*664G>A 3_prime_UTR_variant Exon 11 of 14 2 ENSP00000418214.2 A0A8I5FW65

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152072
Hom.:
0
Cov.:
32
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251072
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135682
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000869
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:
0.00000548
AC:
8
AN:
1459750
Hom.:
0
Cov.:
29
AF XY:
0.00000551
AC XY:
4
AN XY:
726306
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000134
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:
9.01e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152072
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74286
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 23, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1186G>A (p.D396N) alteration is located in exon 10 (coding exon 9) of the LEKR1 gene. This alteration results from a G to A substitution at nucleotide position 1186, causing the aspartic acid (D) at amino acid position 396 to be replaced by an asparagine (N). 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
-0.33
T
BayesDel_noAF
Benign
-0.51
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.063
T;.
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.81
T;T
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Uncertain
2.4
M;.
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-2.4
N;N
REVEL
Benign
0.18
Sift
Uncertain
0.0070
D;D
Sift4G
Uncertain
0.032
D;D
Polyphen
0.56
P;.
Vest4
0.18
MutPred
0.19
Gain of MoRF binding (P = 0.05);.;
MVP
0.25
ClinPred
0.84
D
GERP RS
4.6
Varity_R
0.087

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs761327164; hg19: chr3-156729278; API