6-5261075-T-G

Position:

• chr6-5261075-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000324331.10(FARS2):​c.-305T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00827 in 451,680 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (91 hom., cov: 34)
  • Exomes 𝑓: 0.0022 (23 hom.)
• Consequence: FARS2 ENST00000324331.10 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.23

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 6-5261075-T-G is Benign according to our data. Variant chr6-5261075-T-G is described in ClinVar as [Benign]. Clinvar id is 1233400.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARS2	NM_001318872.2	c.-305T>G		5_prime_UTR_variant	1/7
FARS2	NM_001374878.1	c.-338T>G		5_prime_UTR_variant	1/7
FARS2	XM_047418087.1	c.-305T>G		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARS2	ENST00000324331.10	c.-305T>G		5_prime_UTR_variant	1/7	1		P1

Frequencies

GnomAD3 genomes AF: 0.0203 AC: 3082 AN: 152124 Hom.: 91 Cov.: 34

Gnomad AFR AF: 0.0690

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00808

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00218 AC: 652 AN: 299440 Hom.: 23 Cov.: 6 AF XY: 0.00203 AC XY: 291 AN XY: 143242

Gnomad4 AFR exome AF: 0.0737

Gnomad4 AMR exome AF: 0.0100

Gnomad4 ASJ exome AF: 0.000697

Gnomad4 EAS exome AF: 0.000755

Gnomad4 SAS exome AF: 0.00816

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000291

Gnomad4 OTH exome AF: 0.00419

GnomAD4 genome AF: 0.0203 AC: 3083 AN: 152240 Hom.: 91 Cov.: 34 AF XY: 0.0193 AC XY: 1438 AN XY: 74436

Gnomad4 AFR AF: 0.0688

Gnomad4 AMR AF: 0.00771

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.00809

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00440 Hom.: 3

Bravo AF: 0.0237

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.34

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: rs116440418; hg19: chr6-5261308;