Variant 6-30914857-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020442.6(VARS2):c.21C>T(p.Ala7Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,612,758 control chromosomes in the GnomAD database, including 93,516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6828 hom., cov: 32)

Exomes 𝑓: 0.34 ( 86688 hom. )

Consequence

VARS2
NM_020442.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.184

Variant links:

Genes affected

VARS2 (HGNC:21642): (valyl-tRNA synthetase 2, mitochondrial) This gene encodes a mitochondrial aminoacyl-tRNA synthetase, which catalyzes the attachment of valine to tRNA(Val) for mitochondrial translation. Mutations in this gene cause combined oxidative phosphorylation deficiency-20, and are also associated with early-onset mitochondrial encephalopathies. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2014]

VARS2 links:

ENSG00000288473 (HGNC:):

ENSG00000288473 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 6-30914857-C-T is Benign according to our data. Variant chr6-30914857-C-T is described in ClinVar as [Benign]. Clinvar id is 380149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.184 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VARS2	NM_020442.6 link	c.21C>T	p.Ala7Ala	synonymous_variant	2/30	ENST00000676266.1	NP_065175.4	Q5ST30-1B4E0K6B4DG77
VARS2	NM_001167734.2 link	c.111C>T	p.Ala37Ala	synonymous_variant	2/30		NP_001161206.1	Q5ST30-4A0A1U9X9B3
VARS2	NM_001167733.3 link	c.-219-299C>T		intron_variant			NP_001161205.1	Q5ST30-3B4E0K6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VARS2	ENST00000676266.1 link	c.21C>T	p.Ala7Ala	synonymous_variant	2/30		NM_020442.6	ENSP00000502585.1		Q5ST30-1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42528

AN:

151942

Hom.:

6831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.379

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.283

GnomAD3 exomes

AF:

0.316

AC:

77929

AN:

246428

Hom.:

13178

AF XY:

0.324

AC XY:

43513

AN XY:

134366

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.381

Gnomad EAS exome

AF:

0.283

Gnomad SAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.369

Gnomad OTH exome

AF:

0.334

GnomAD4 exome

AF:

0.339

AC:

495673

AN:

1460696

Hom.:

86688

Cov.:

AF XY:

0.339

AC XY:

246474

AN XY:

726678

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.220

Gnomad4 ASJ exome

AF:

0.375

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.386

Gnomad4 NFE exome

AF:

0.358

Gnomad4 OTH exome

AF:

0.311

GnomAD4 genome

AF:

0.280

AC:

42538

AN:

152062

Hom.:

6828

Cov.:

AF XY:

0.281

AC XY:

20858

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.124

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.401

Gnomad4 EAS

AF:

0.254

Gnomad4 SAS

AF:

0.263

Gnomad4 FIN

AF:

0.392

Gnomad4 NFE

AF:

0.362

Gnomad4 OTH

AF:

0.280

Alfa

AF:

0.346

Hom.:

12105

Bravo

AF:

0.263

Asia WGS

AF:

0.207

AC:

724

AN:

3478

EpiCase

AF:

0.369

EpiControl

AF:

0.372

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 16, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 31, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 48% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 45. Only high quality variants are reported. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 19, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.3

DANN

Benign

0.90

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over