Genetic Variant LENG9:p.Ala409Thr (chr19-54462302-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001301782.2(LENG9):c.1225G>A(p.Ala409Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000363 in 1,602,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00036 ( 0 hom. )

Consequence

LENG9
NM_001301782.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.326

Variant links:

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]

LENG9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011418879).

BS2

High AC in GnomAd4 at 52 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LENG9	NM_001301782.2 link	c.1225G>A	p.Ala409Thr	missense_variant	Exon 1 of 1	ENST00000611161.2	NP_001288711.1	A0A087WVD1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LENG9	ENST00000611161.2 link	c.1225G>A	p.Ala409Thr	missense_variant	Exon 1 of 1	6	NM_001301782.2	ENSP00000479355.1		A0A087WVD1

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000379

AC:

AN:

243060

Hom.:

AF XY:

0.000335

AC XY:

AN XY:

131162

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000476

Gnomad NFE exome

AF:

0.000465

Gnomad OTH exome

AF:

0.000509

GnomAD4 exome

AF:

0.000365

AC:

529

AN:

1449888

Hom.:

Cov.:

AF XY:

0.000338

AC XY:

243

AN XY:

719660

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.00104

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000208

Gnomad4 NFE exome

AF:

0.000400

Gnomad4 OTH exome

AF:

0.000452

GnomAD4 genome

AF:

0.000341

AC:

AN:

152370

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000531

Hom.:

Bravo

AF:

0.000476

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000296

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1294G>A (p.A432T) alteration is located in exon 1 (coding exon 1) of the LENG9 gene. This alteration results from a G to A substitution at nucleotide position 1294, causing the alanine (A) at amino acid position 432 to be replaced by a threonine (T). 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

-0.33

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.056

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.14

M_CAP

Benign

0.026

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.32

Sift4G

Benign

0.24

Vest4

0.28

MVP

0.030

ClinPred

0.078

GERP RS

1.3

gMVP

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over