chr19-54462302-C-T

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

1
12

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]

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
LENG9NM_001301782.2 linkc.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
LENG9ENST00000611161.2 linkc.1225G>A p.Ala409Thr missense_variant Exon 1 of 1 6 NM_001301782.2 ENSP00000479355.1 A0A087WVD1

Frequencies

GnomAD3 genomes
AF:
0.000342
AC:
52
AN:
152252
Hom.:
0
Cov.:
33
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:
92
AN:
243060
Hom.:
0
AF XY:
0.000335
AC XY:
44
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.:
0
Cov.:
69
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:
52
AN:
152370
Hom.:
0
Cov.:
33
AF XY:
0.000376
AC XY:
28
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.:
0
Bravo
AF:
0.000476
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000296
AC:
36

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
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.056
T
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.14
N
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.011
T
MetaSVM
Benign
-0.95
T
PrimateAI
Benign
0.32
T
Sift4G
Benign
0.24
T
Vest4
0.28
MVP
0.030
ClinPred
0.078
T
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.

Other links and lift over

dbSNP: rs115358813; hg19: chr19-54973482; API