chr6-31778997-C-T
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7
The NM_006295.3(VARS1):c.3696G>A(p.Pro1232Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,613,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000058 ( 0 hom. )
Consequence
VARS1
NM_006295.3 synonymous
NM_006295.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.532
Genes affected
VARS1 (HGNC:12651): (valyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. The protein encoded by this gene belongs to class-I aminoacyl-tRNA synthetase family and is located in the class III region of the major histocompatibility complex. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP7
Synonymous conserved (PhyloP=0.532 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VARS1 | NM_006295.3 | c.3696G>A | p.Pro1232Pro | synonymous_variant | Exon 29 of 30 | ENST00000375663.8 | NP_006286.1 | |
VARS1 | XM_005249362.3 | c.3699G>A | p.Pro1233Pro | synonymous_variant | Exon 29 of 30 | XP_005249419.1 | ||
VARS1 | XM_047419296.1 | c.3699G>A | p.Pro1233Pro | synonymous_variant | Exon 28 of 29 | XP_047275252.1 | ||
VARS1 | XM_047419297.1 | c.3696G>A | p.Pro1232Pro | synonymous_variant | Exon 28 of 29 | XP_047275253.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VARS1 | ENST00000375663.8 | c.3696G>A | p.Pro1232Pro | synonymous_variant | Exon 29 of 30 | 1 | NM_006295.3 | ENSP00000364815.3 | ||
Y_RNA | ENST00000364685.1 | n.-92G>A | upstream_gene_variant | 6 | ||||||
VARS1 | ENST00000463184.1 | n.*233G>A | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152238Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
26
AN:
152238
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000779 AC: 19AN: 243966Hom.: 0 AF XY: 0.0000749 AC XY: 10AN XY: 133462
GnomAD3 exomes
AF:
AC:
19
AN:
243966
Hom.:
AF XY:
AC XY:
10
AN XY:
133462
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000582 AC: 85AN: 1460690Hom.: 0 Cov.: 32 AF XY: 0.0000578 AC XY: 42AN XY: 726648
GnomAD4 exome
AF:
AC:
85
AN:
1460690
Hom.:
Cov.:
32
AF XY:
AC XY:
42
AN XY:
726648
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000171 AC: 26AN: 152356Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74508
GnomAD4 genome
AF:
AC:
26
AN:
152356
Hom.:
Cov.:
32
AF XY:
AC XY:
12
AN XY:
74508
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Oct 15, 2024
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
BP4 -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at