6-5261370-T-C

Variant summary

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

The ENST00000324331.10(FARS2):c.-22+12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,014 control chromosomes in the GnomAD database, including 11,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (11732 hom., cov: 33)
  • Exomes 𝑓: 0.19 (9 hom.)
  • Failed GnomAD Quality Control
• Consequence: FARS2 ENST00000324331.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.445

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=-0.88).
• BP6: Variant 6-5261370-T-C is Benign according to our data. Variant chr6-5261370-T-C is described in ClinVar as [Benign]. Clinvar id is 1243161.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARS2	NM_001374878.1	c.-43T>C		5_prime_UTR_variant	1/7
FARS2	NM_001318872.2	c.-22+12T>C		intron_variant
FARS2	XM_047418086.1	c.-22+11417T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARS2	ENST00000324331.10	c.-22+12T>C		intron_variant		1		P1
FARS2	ENST00000602691.1	c.-376T>C		5_prime_UTR_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54214 AN: 151896 Hom.: 11699 Cov.: 33

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.354

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.186 AC: 87 AN: 468 Hom.: 9 Cov.: 0 AF XY: 0.179 AC XY: 62 AN XY: 346

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.0833

GnomAD4 genome AF: 0.357 AC: 54304 AN: 152014 Hom.: 11732 Cov.: 33 AF XY: 0.351 AC XY: 26077 AN XY: 74332

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.351

Alfa AF: 0.313 Hom.: 1088

Bravo AF: 0.382

Asia WGS AF: 0.244 AC: 851 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

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.4
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17139985; hg19: chr6-5261603;