rs17140129

Positions:

• chr6-5298129-A-G

Variant summary

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

The ENST00000274680.9(FARS2):​c.-22+36469A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,200 control chromosomes in the GnomAD database, including 2,006 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 0.15 (2006 hom., cov: 33)
• Consequence: FARS2 ENST00000274680.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FARS2	NM_006567.5	c.-22+36469A>G		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+36469A>G		intron_variant		1	NM_006567.5	ENSP00000274680	P1
FARS2	ENST00000324331.10	c.-22+36771A>G		intron_variant		1		ENSP00000316335	P1
FARS2	ENST00000602691.1	c.-22+25640A>G		intron_variant		3		ENSP00000473394
FARS2	ENST00000648580.1	c.-22+36469A>G		intron_variant, NMD_transcript_variant				ENSP00000497889

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23460 AN: 152082 Hom.: 1999 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.154 AC: 23499 AN: 152200 Hom.: 2006 Cov.: 33 AF XY: 0.150 AC XY: 11170 AN XY: 74408

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.148

Alfa AF: 0.146 Hom.: 401

Bravo AF: 0.157

Asia WGS AF: 0.125 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0050
DANN	Benign	0.66

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: rs17140129; hg19: chr6-5298362;