rs6597161

Variant names:

• chr6-5734974-C-A
• rs6597161
• NM_006567.5:c.1218-36317C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-5734974-C-A
• chr6-5734974-C-G
• chr6-5734974-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

FARS2 Gene-Disease associations (from GenCC):

• metabolic disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• combined oxidative phosphorylation defect type 14

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hereditary spastic paraplegia 77

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006567.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARS2	NM_006567.5	MANE Select	c.1218-36317C>A		intron	N/A	NP_006558.1	O95363
	FARS2	NM_001318872.2		c.1218-36317C>A		intron	N/A	NP_001305801.1	O95363
	FARS2	NM_001374875.1		c.1218-36317C>A		intron	N/A	NP_001361804.1	O95363

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARS2	ENST00000274680.9	TSL:1 MANE Select	c.1218-36317C>A		intron	N/A	ENSP00000274680.4	O95363
	FARS2	ENST00000324331.10	TSL:1	c.1218-36317C>A		intron	N/A	ENSP00000316335.5	O95363
	FARS2	ENST00000897566.1		c.1218-36317C>A		intron	N/A	ENSP00000567625.1

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

African (AFR) AF: 0.662 AC: 27462 AN: 41462

American (AMR) AF: 0.658 AC: 10059 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1960 AN: 3472

East Asian (EAS) AF: 0.838 AC: 4331 AN: 5166

South Asian (SAS) AF: 0.719 AC: 3463 AN: 4818

European-Finnish (FIN) AF: 0.614 AC: 6493 AN: 10568

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39638 AN: 67960

Other (OTH) AF: 0.631 AC: 1331 AN: 2108

Alfa AF: 0.601 Hom.: 41411

Bravo AF: 0.634

Asia WGS AF: 0.760 AC: 2638 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.17
DANN	Benign	0.85
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6597161; hg19: chr6-5735207;