19-54462340-A-G

Variant names:

• chr19-54462340-A-G
• NM_001301782.2:c.1187T>C

Variant summary

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

The NM_001301782.2(LENG9):​c.1187T>C​(p.Leu396Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,188 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LENG9 NM_001301782.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54

Genes affected

LENG9 (HGNC:16306): (leukocyte receptor cluster member 9) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LENG9	NM_001301782.2	c.1187T>C	p.Leu396Pro	missense_variant	Exon 1 of 1	ENST00000611161.2	NP_001288711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LENG9	ENST00000611161.2	c.1187T>C	p.Leu396Pro	missense_variant	Exon 1 of 1	6	NM_001301782.2	ENSP00000479355.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456188 Hom.: 0 Cov.: 69 AF XY: 0.00000138 AC XY: 1 AN XY: 723624

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: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1256T>C (p.L419P) alteration is located in exon 1 (coding exon 1) of the LENG9 gene. This alteration results from a T to C substitution at nucleotide position 1256, causing the leucine (L) at amino acid position 419 to be replaced by a proline (P). 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	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	17
DANN	Benign	0.63
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.059	N
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.60	T
PrimateAI	Uncertain	0.50	T
Sift4G	Benign	0.095	T
Vest4		0.70
MVP		0.20
ClinPred		0.38	T
GERP RS		2.7
gMVP		0.87

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54973520;