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GeneBe

13-27556336-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_153371.4(LNX2):c.1446C>T(p.Thr482=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 1,613,920 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 27 hom., cov: 32)
Exomes 𝑓: 0.0017 ( 22 hom. )

Consequence

LNX2
NM_153371.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.26
Variant links:
Genes affected
LNX2 (HGNC:20421): (ligand of numb-protein X 2) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in protein ubiquitination. [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 -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 13-27556336-G-A is Benign according to our data. Variant chr13-27556336-G-A is described in ClinVar as [Benign]. Clinvar id is 776786.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.26 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1530/152166) while in subpopulation AFR AF= 0.0314 (1302/41514). AF 95% confidence interval is 0.0299. There are 27 homozygotes in gnomad4. There are 748 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 27 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LNX2NM_153371.4 linkuse as main transcriptc.1446C>T p.Thr482= synonymous_variant 7/10 ENST00000316334.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LNX2ENST00000316334.5 linkuse as main transcriptc.1446C>T p.Thr482= synonymous_variant 7/101 NM_153371.4 P1
LNX2ENST00000649248.1 linkuse as main transcriptc.1446C>T p.Thr482= synonymous_variant 8/11 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0101
AC:
1530
AN:
152048
Hom.:
27
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0315
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00747
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0348
Gnomad NFE
AF:
0.00116
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00340
AC:
853
AN:
250940
Hom.:
5
AF XY:
0.00264
AC XY:
358
AN XY:
135600
show subpopulations
Gnomad AFR exome
AF:
0.0330
Gnomad AMR exome
AF:
0.00457
Gnomad ASJ exome
AF:
0.000795
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000359
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00103
Gnomad OTH exome
AF:
0.00360
GnomAD4 exome
AF:
0.00171
AC:
2498
AN:
1461754
Hom.:
22
Cov.:
31
AF XY:
0.00160
AC XY:
1165
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.0338
Gnomad4 AMR exome
AF:
0.00501
Gnomad4 ASJ exome
AF:
0.000804
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000359
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000682
Gnomad4 OTH exome
AF:
0.00421
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0101
AC:
1530
AN:
152166
Hom.:
27
Cov.:
32
AF XY:
0.0101
AC XY:
748
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.0314
Gnomad4 AMR
AF:
0.00746
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00116
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00605
Hom.:
2
Bravo
AF:
0.0120
Asia WGS
AF:
0.00202
AC:
7
AN:
3476
EpiCase
AF:
0.00153
EpiControl
AF:
0.00184

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
Cadd
Benign
1.3
Dann
Benign
0.55
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs115119970; hg19: chr13-28130473; API