chr3-156920585-G-A

Position:

• chr3-156920585-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004316.3(LEKR1):​c.274G>A​(p.Val92Ile) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LEKR1 NM_001004316.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0210

Genes affected

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

LEKR1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058209807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEKR1	NM_001004316.3	c.274G>A	p.Val92Ile	missense_variant	4/13	ENST00000356539.9	NP_001004316.2
LEKR1	NM_001193283.2	c.274G>A	p.Val92Ile	missense_variant	4/5		NP_001180212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEKR1	ENST00000356539.9	c.274G>A	p.Val92Ile	missense_variant	4/13	5	NM_001004316.3	ENSP00000348936.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1309292 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 648232

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Aug 14, 2024

The c.274G>A (p.V92I) alteration is located in exon 4 (coding exon 3) of the LEKR1 gene. This alteration results from a G to A substitution at nucleotide position 274, causing the valine (V) at amino acid position 92 to be replaced by an isoleucine (I). 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	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.9
DANN	Benign	0.66
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.52	T;.;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.14	N;N;.
REVEL	Benign	0.0070
Sift	Benign	0.51	T;T;.
Sift4G	Benign	0.59	T;T;T
Polyphen		0.0050	.;B;B
Vest4		0.13
MutPred		0.16		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.014
ClinPred		0.060	T
GERP RS		-0.39
gMVP		0.0081

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: chr3-156638374;