Variant rs3740487 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_001163812.2(TWNK):c.*1C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,613,746 control chromosomes in the GnomAD database, including 51,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7580 hom., cov: 32)

Exomes 𝑓: 0.23 ( 44061 hom. )

Consequence

TWNK
NM_001163812.2 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.952

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:

TWNK (HGNC:):

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=-0.81).

BP6

Variant 10-100991026-C-A is Benign according to our data. Variant chr10-100991026-C-A is described in ClinVar as [Benign]. Clinvar id is 136591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 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+16C>A		intron_variant		ENST00000311916.8	NP_068602.2	Q96RR1-1E5KSY5Q9H6V3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TWNK	ENST00000311916.8 linkuse as main transcript	c.1734+16C>A		intron_variant		1	NM_021830.5	ENSP00000309595.2		Q96RR1-1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43985

AN:

151996

Hom.:

7556

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:

0.544

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.267

GnomAD3 exomes

AF:

0.274

AC:

68942

AN:

251318

Hom.:

11208

AF XY:

0.266

AC XY:

36064

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.444

Gnomad AMR exome

AF:

0.374

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.550

Gnomad SAS exome

AF:

0.294

Gnomad FIN exome

AF:

0.174

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.246

GnomAD4 exome

AF:

0.231

AC:

337875

AN:

1461632

Hom.:

44061

Cov.:

AF XY:

0.231

AC XY:

168143

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.470

Gnomad4 AMR exome

AF:

0.365

Gnomad4 ASJ exome

AF:

0.139

Gnomad4 EAS exome

AF:

0.554

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.179

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.290

AC:

44056

AN:

152114

Hom.:

7580

Cov.:

AF XY:

0.291

AC XY:

21642

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.445

Gnomad4 AMR

AF:

0.304

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.544

Gnomad4 SAS

AF:

0.305

Gnomad4 FIN

AF:

0.174

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.269

Alfa

AF:

0.196

Hom.:

1902

Bravo

AF:

0.310

Asia WGS

AF:

0.422

AC:

1466

AN:

3478

EpiCase

AF:

0.196

EpiControl

AF:

0.204

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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 30, 2011	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.0

DANN

Benign

0.69

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