6-5288973-G-A

Position:

• chr6-5288973-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006567.5(FARS2):​c.-22+27313G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,138 control chromosomes in the GnomAD database, including 47,932 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (47932 hom., cov: 32)
• Consequence: FARS2 NM_006567.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FARS2	NM_006567.5	c.-22+27313G>A		intron_variant		ENST00000274680.9	NP_006558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FARS2	ENST00000274680.9	c.-22+27313G>A		intron_variant		1	NM_006567.5	ENSP00000274680	P1
FARS2	ENST00000324331.10	c.-22+27615G>A		intron_variant		1		ENSP00000316335	P1
FARS2	ENST00000602691.1	c.-22+16484G>A		intron_variant		3		ENSP00000473394
FARS2	ENST00000648580.1	c.-22+27313G>A		intron_variant, NMD_transcript_variant				ENSP00000497889

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119561 AN: 152022 Hom.: 47870 Cov.: 32

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.760

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.787 AC: 119676 AN: 152138 Hom.: 47932 Cov.: 32 AF XY: 0.787 AC XY: 58531 AN XY: 74368

Gnomad4 AFR AF: 0.944

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.830

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.761

Alfa AF: 0.752 Hom.: 5080

Bravo AF: 0.793

Asia WGS AF: 0.828 AC: 2878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.36

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

Other links and lift over

dbSNP: rs2326584; hg19: chr6-5289206;