19-54462205-A-C

Variant names:

• chr19-54462205-A-C
• rs746679553
• NM_001301782.2:c.1322T>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001301782.2(LENG9):​c.1322T>G​(p.Leu441Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,234 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (1 hom.)
• Consequence: LENG9 NM_001301782.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19

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]

LENG8 (HGNC:15500): (leukocyte receptor cluster member 8) Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.064658344).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LENG9	NM_001301782.2	c.1322T>G	p.Leu441Arg	missense_variant	Exon 1 of 1	ENST00000611161.2	NP_001288711.1
LENG8	NM_052925.4	c.*1277A>C		downstream_gene_variant		ENST00000326764.10	NP_443157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LENG9	ENST00000611161.2	c.1322T>G	p.Leu441Arg	missense_variant	Exon 1 of 1	6	NM_001301782.2	ENSP00000479355.1
LENG8	ENST00000326764.10	c.*1277A>C		downstream_gene_variant		1	NM_052925.4	ENSP00000318374.5
LENG8	ENST00000610347.1	c.*3299A>C		downstream_gene_variant		5		ENSP00000478590.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461234 Hom.: 1 Cov.: 68 AF XY: 0.00000825 AC XY: 6 AN XY: 726846

Gnomad4 AFR exome AF: 0.000149

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: 0.0000663

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1391T>G (p.L464R) alteration is located in exon 1 (coding exon 1) of the LENG9 gene. This alteration results from a T to G substitution at nucleotide position 1391, causing the leucine (L) at amino acid position 464 to be replaced by an arginine (R). 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	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.28	T
Sift4G	Benign	0.11	T
Vest4		0.12
MVP		0.11
ClinPred		0.13	T
GERP RS		2.6
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs746679553; hg19: chr19-54973385;