rs6597161

chr6-5734974-C-Achr6-5734974-C-Gchr6-5734974-C-T

Variant summary

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

The NM_006567.5(FARS2):c.1218-36317C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,048 control chromosomes in the GnomAD database, including 30,140 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 0.63 (30140 hom., cov: 32)
• Consequence: FARS2 NM_006567.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARS2	NM_006567.5	c.1218-36317C>A		intron_variant		ENST00000274680.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARS2	ENST00000274680.9	c.1218-36317C>A		intron_variant		1	NM_006567.5	P1
FARS2	ENST00000324331.10	c.1218-36317C>A		intron_variant		1		P1
FARS2	ENST00000648580.1	c.1218-86734C>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95388 AN: 151930 Hom.: 30103 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.628 AC: 95478 AN: 152048 Hom.: 30140 Cov.: 32 AF XY: 0.636 AC XY: 47265 AN XY: 74318

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.631

Alfa AF: 0.594 Hom.: 27763

Bravo AF: 0.634

Asia WGS AF: 0.760 AC: 2638 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.17
Dann	Benign	0.85

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: rs6597161; hg19: chr6-5735207;