chr3-157028301-G-A

Position:

• chr3-157028301-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004316.3(LEKR1):​c.1567G>A​(p.Glu523Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/17 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)
• Consequence: LEKR1 NM_001004316.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48

Genes affected

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

ACMG classification

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=0.070773125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEKR1	NM_001004316.3	c.1567G>A	p.Glu523Lys	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	c.1567G>A	p.Glu523Lys	missense_variant	12/13	5	NM_001004316.3	ENSP00000348936.4
LEKR1	ENST00000470811.6	n.*1045G>A		non_coding_transcript_exon_variant	13/14	2		ENSP00000418214.2
LEKR1	ENST00000470811.6	n.*1045G>A		3_prime_UTR_variant	13/14	2		ENSP00000418214.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.1567G>A (p.E523K) alteration is located in exon 12 (coding exon 11) of the LEKR1 gene. This alteration results from a G to A substitution at nucleotide position 1567, causing the glutamic acid (E) at amino acid position 523 to be replaced by a lysine (K). 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	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.080
Sift	Benign	0.22	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.0020	B;.
Vest4		0.15
MutPred		0.28		Gain of ubiquitination at E219 (P = 0.0045);.;
MVP		0.095
ClinPred		0.28	T
GERP RS		0.030
Varity_R		0.075

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-156746090; COSMIC: COSV62960881;