chr6-30914336-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_020442.6(VARS2):c.-36G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000993 in 1,218,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

VARS2
NM_020442.6 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.06

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:

GTF2H4 (HGNC:4658): (general transcription factor IIH subunit 4) Enables RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in nuclear speck. Part of core TFIIH complex portion of holo TFIIH complex and transcription factor TFIID complex. [provided by Alliance of Genome Resources, Apr 2022]

GTF2H4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 6-30914336-G-A is Benign according to our data. Variant chr6-30914336-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 507743.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00046 (70/152178) while in subpopulation AFR AF= 0.0015 (62/41428). AF 95% confidence interval is 0.0012. There are 0 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
VARS2	NM_020442.6 link	c.-36G>A	5_prime_UTR_variant	Exon 1 of 30	ENST00000676266.1	NP_065175.4	Q5ST30-1B4E0K6B4DG77
VARS2	NM_001167734.2 link	c.-76G>A	5_prime_UTR_variant	Exon 1 of 30		NP_001161206.1	Q5ST30-4A0A1U9X9B3
VARS2	NM_001167733.3 link	c.-228G>A	5_prime_UTR_variant	Exon 1 of 29		NP_001161205.1	Q5ST30-3B4E0K6
GTF2H4	NM_001517.5 link	c.*353G>A	downstream_gene_variant		ENST00000259895.9	NP_001508.1	Q92759-1A0A1U9X7S4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VARS2	ENST00000676266 link	c.-36G>A		5_prime_UTR_variant	Exon 1 of 30		NM_020442.6	ENSP00000502585.1		Q5ST30-1
GTF2H4	ENST00000259895.9 link	c.*353G>A		downstream_gene_variant		1	NM_001517.5	ENSP00000259895.4		Q92759-1

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD4 exome

AF:

0.0000478

AC:

AN:

1066664

Hom.:

Cov.:

AF XY:

0.0000415

AC XY:

AN XY:

505992

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.000467

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000133

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000221

Gnomad4 OTH exome

AF:

0.000207

GnomAD4 genome

AF:

0.000460

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00150

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000498

Hom.:

Bravo

AF:

0.000574

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 16, 2017

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.82

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.5

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