rs1554169338

Positions:

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_006567.5(FARS2):ā€‹c.354A>Gā€‹(p.Pro118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,886 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 Likely benign (ā˜…ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000068 ( 0 hom. )

Consequence

FARS2
NM_006567.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.80
Variant links:
Genes affected
FARS2 (HGNC:21062): (phenylalanyl-tRNA synthetase 2, mitochondrial) This gene encodes a protein that transfers phenylalanine to its cognate tRNA. This protein localizes to the mitochondrion and plays a role in mitochondrial protein translation. Mutations in this gene can cause combined oxidative phosphorylation deficiency 14 (Alpers encephalopathy). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 6-5368924-A-G is Benign according to our data. Variant chr6-5368924-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 516063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.8 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FARS2NM_006567.5 linkuse as main transcriptc.354A>G p.Pro118= synonymous_variant 2/7 ENST00000274680.9 NP_006558.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FARS2ENST00000274680.9 linkuse as main transcriptc.354A>G p.Pro118= synonymous_variant 2/71 NM_006567.5 ENSP00000274680 P1
FARS2ENST00000324331.10 linkuse as main transcriptc.354A>G p.Pro118= synonymous_variant 2/71 ENSP00000316335 P1
FARS2ENST00000648580.1 linkuse as main transcriptc.354A>G p.Pro118= synonymous_variant, NMD_transcript_variant 2/9 ENSP00000497889

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461886
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
727244
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:
0.00000809
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Combined oxidative phosphorylation defect type 14 Benign:2
Likely benign, criteria provided, single submitterclinical testingWong Mito Lab, Molecular and Human Genetics, Baylor College of MedicineJun 13, 2018- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 08, 2019- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxMar 31, 2017This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.34
DANN
Benign
0.65

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: rs1554169338; hg19: chr6-5369157; API