6-31573497-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000595.4(LTA):ā€‹c.422A>Gā€‹(p.Gln141Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

LTA
NM_000595.4 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.463
Variant links:
Genes affected
LTA (HGNC:6709): (lymphotoxin alpha) The encoded protein, a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. The protein is highly inducible, secreted, and forms heterotrimers with lymphotoxin-beta which anchor lymphotoxin-alpha to the cell surface. This protein also mediates a large variety of inflammatory, immunostimulatory, and antiviral responses, is involved in the formation of secondary lymphoid organs during development and plays a role in apoptosis. Genetic variations in this gene are associated with susceptibility to leprosy type 4, myocardial infarction, non-Hodgkin's lymphoma, and psoriatic arthritis. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13813245).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LTANM_000595.4 linkc.422A>G p.Gln141Arg missense_variant Exon 4 of 4 ENST00000418386.3 NP_000586.2 P01374Q5STV3
LTANM_001159740.2 linkc.422A>G p.Gln141Arg missense_variant Exon 4 of 4 NP_001153212.1 P01374Q5STV3
LTAXM_047418773.1 linkc.422A>G p.Gln141Arg missense_variant Exon 6 of 6 XP_047274729.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LTAENST00000418386.3 linkc.422A>G p.Gln141Arg missense_variant Exon 4 of 4 1 NM_000595.4 ENSP00000413450.2 P01374
LTAENST00000454783.5 linkc.422A>G p.Gln141Arg missense_variant Exon 4 of 4 2 ENSP00000403495.1 P01374
LTAENST00000471842.1 linkn.670A>G non_coding_transcript_exon_variant Exon 3 of 3 2
LTAENST00000489638.5 linkn.550A>G non_coding_transcript_exon_variant Exon 3 of 3 5

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251370
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135844
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461860
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727232
show subpopulations
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
14
DANN
Benign
0.94
DEOGEN2
Uncertain
0.57
D;D
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.38
N
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.083
Sift
Benign
0.099
T;T
Sift4G
Benign
0.50
T;T
Polyphen
0.0
B;B
Vest4
0.055
MutPred
0.64
Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP
0.38
MPC
0.93
ClinPred
0.038
T
GERP RS
0.17
Varity_R
0.19
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs201957060; hg19: chr6-31541274; API