NM_001004316.3:c.1528C>G

Variant names:

• chr3-157028262-C-G
• rs766522161
• NM_001004316.3:c.1528C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001004316.3(LEKR1):​c.1528C>G​(p.Arg510Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000089 in 1,461,284 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R510C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: LEKR1 NM_001004316.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.82
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004316.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEKR1	NM_001004316.3	MANE Select	c.1528C>G	p.Arg510Gly	missense	Exon 12 of 13	NP_001004316.2	J3KP02

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEKR1	ENST00000356539.9	TSL:5 MANE Select	c.1528C>G	p.Arg510Gly	missense	Exon 12 of 13	ENSP00000348936.4	J3KP02
	LEKR1	ENST00000470811.6	TSL:2	n.*1006C>G		non_coding_transcript_exon	Exon 13 of 14	ENSP00000418214.2	A0A8I5FW65
	LEKR1	ENST00000470811.6	TSL:2	n.*1006C>G		3_prime_UTR	Exon 13 of 14	ENSP00000418214.2	A0A8I5FW65

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1461284 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 726930

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111722

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.8
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.14
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.31	T
Polyphen		1.0	D
Vest4		0.50
MutPred		0.13		Loss of MoRF binding (P = 0.0738)
MVP		0.49
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.27
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs766522161; hg19: chr3-156746051;