NM_006567.5:c.1344G>C

Variant names:

• chr6-5771417-G-C
• NM_006567.5:c.1344G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006567.5(FARS2):​c.1344G>C​(p.Glu448Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: FARS2 NM_006567.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34771848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FARS2	NM_006567.5	c.1344G>C	p.Glu448Asp	missense_variant	Exon 7 of 7	ENST00000274680.9	NP_006558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARS2	ENST00000274680.9	c.1344G>C	p.Glu448Asp	missense_variant	Exon 7 of 7	1	NM_006567.5	ENSP00000274680.4
FARS2	ENST00000324331.10	c.1344G>C	p.Glu448Asp	missense_variant	Exon 7 of 7	1		ENSP00000316335.5
FARS2	ENST00000648580.1	n.1218-50291G>C		intron_variant	Intron 6 of 8			ENSP00000497889.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461568 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727076

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.0044	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D;D
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.6	N;N
REVEL	Uncertain	0.41
Sift	Benign	0.056	T;T
Sift4G	Uncertain	0.028	D;D
Polyphen		0.60	P;P
Vest4		0.38
MutPred		0.43		Loss of disorder (P = 0.1501);Loss of disorder (P = 0.1501);
MVP		0.97
MPC		0.14
ClinPred		0.46	T
GERP RS		2.8
Varity_R		0.39
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-5771650;