Variant rs3824783 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021830.5(TWNK):c.1734+84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,592,014 control chromosomes in the GnomAD database, including 50,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7586 hom., cov: 32)

Exomes 𝑓: 0.23 ( 43259 hom. )

Consequence

TWNK
NM_021830.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.677

Variant links:

Genes affected

TWNK (HGNC:1160): (twinkle mtDNA helicase) This gene encodes a hexameric DNA helicase which unwinds short stretches of double-stranded DNA in the 5' to 3' direction and, along with mitochondrial single-stranded DNA binding protein and mtDNA polymerase gamma, is thought to play a key role in mtDNA replication. The protein localizes to the mitochondrial matrix and mitochondrial nucleoids. Mutations in this gene cause infantile onset spinocerebellar ataxia (IOSCA) and progressive external ophthalmoplegia (PEO) and are also associated with several mitochondrial depletion syndromes. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Aug 2009]

TWNK links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 10-100991094-G-A is Benign according to our data. Variant chr10-100991094-G-A is described in ClinVar as [Benign]. Clinvar id is 1252118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TWNK	NM_021830.5 linkuse as main transcript	c.1734+84G>A		intron_variant		ENST00000311916.8	NP_068602.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TWNK	ENST00000311916.8 linkuse as main transcript	c.1734+84G>A		intron_variant		1	NM_021830.5	ENSP00000309595	P1	Q96RR1-1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43995

AN:

151980

Hom.:

7562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.445

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.546

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.266

GnomAD4 exome

AF:

0.231

AC:

332428

AN:

1439916

Hom.:

43259

Cov.:

AF XY:

0.231

AC XY:

165121

AN XY:

714714

show subpopulations

Gnomad4 AFR exome

AF:

0.471

Gnomad4 AMR exome

AF:

0.364

Gnomad4 ASJ exome

AF:

0.139

Gnomad4 EAS exome

AF:

0.553

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.180

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.246

GnomAD4 genome

AF:

0.290

AC:

44066

AN:

152098

Hom.:

7586

Cov.:

AF XY:

0.291

AC XY:

21635

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.445

Gnomad4 AMR

AF:

0.304

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.546

Gnomad4 SAS

AF:

0.305

Gnomad4 FIN

AF:

0.173

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.262

Hom.:

1278

Bravo

AF:

0.310

Asia WGS

AF:

0.421

AC:

1465

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.8

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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