3-156942645-A-G

Variant names:

• chr3-156942645-A-G
• rs957340843
• NM_001004316.3:c.676A>G

Variant summary

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

The NM_001004316.3(LEKR1):​c.676A>G​(p.Ile226Val) 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. 11/15 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: 0.0000027 (0 hom.)
• Consequence: LEKR1 NM_001004316.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61

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=0.10499382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LEKR1	NM_001004316.3	c.676A>G	p.Ile226Val	missense_variant	Exon 6 of 13	ENST00000356539.9	NP_001004316.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LEKR1	ENST00000356539.9	c.676A>G	p.Ile226Val	missense_variant	Exon 6 of 13	5	NM_001004316.3	ENSP00000348936.4
LEKR1	ENST00000470811.6	n.676A>G		non_coding_transcript_exon_variant	Exon 6 of 14	2		ENSP00000418214.2
LEKR1	ENST00000489350.5	n.377A>G		non_coding_transcript_exon_variant	Exon 4 of 5	3
LEKR1	ENST00000495252.1	n.321A>G		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000268 AC: 3 AN: 1119140 Hom.: 0 Cov.: 28 AF XY: 0.00000364 AC XY: 2 AN XY: 549058

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: 0.00000328

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.013
Sift	Benign	0.040	D
Sift4G	Benign	0.15	T
Vest4		0.21
MutPred		0.25		Loss of catalytic residue at I226 (P = 0.0474);
MVP		0.13
ClinPred		0.70	D
GERP RS		5.4

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

Other links and lift over

dbSNP: rs957340843; hg19: chr3-156660434;