Variant chr6-158170446-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_207118.3(GTF2H5):c.-34-24A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 1,365,594 control chromosomes in the GnomAD database, including 2,916 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.043 ( 382 hom., cov: 32)

Exomes 𝑓: 0.043 ( 2534 hom. )

Consequence

GTF2H5
NM_207118.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.636

Variant links:

Genes affected

GTF2H5 (HGNC:21157): (general transcription factor IIH subunit 5) This gene encodes a subunit of transcription/repair factor TFIIH, which functions in gene transcription and DNA repair. This protein stimulates ERCC3/XPB ATPase activity to trigger DNA opening during DNA repair, and is implicated in regulating cellular levels of TFIIH. Mutations in this gene result in trichothiodystrophy, complementation group A. [provided by RefSeq, Mar 2009]

GTF2H5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 6-158170446-A-G is Benign according to our data. Variant chr6-158170446-A-G is described in ClinVar as [Benign]. Clinvar id is 1270314.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF2H5	NM_207118.3 linkuse as main transcript	c.-34-24A>G		intron_variant		ENST00000607778.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF2H5	ENST00000607778.2 linkuse as main transcript	c.-34-24A>G		intron_variant		1	NM_207118.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0434

AC:

6602

AN:

152150

Hom.:

379

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00958

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0207

Gnomad FIN

AF:

0.0576

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0387

Gnomad OTH

AF:

0.0497

GnomAD4 exome

AF:

0.0429

AC:

52006

AN:

1213326

Hom.:

2534

Cov.:

AF XY:

0.0412

AC XY:

25390

AN XY:

616420

show subpopulations

Gnomad4 AFR exome

AF:

0.00775

Gnomad4 AMR exome

AF:

0.268

Gnomad4 ASJ exome

AF:

0.0168

Gnomad4 EAS exome

AF:

0.00104

Gnomad4 SAS exome

AF:

0.0218

Gnomad4 FIN exome

AF:

0.0620

Gnomad4 NFE exome

AF:

0.0366

Gnomad4 OTH exome

AF:

0.0376

GnomAD4 genome

AF:

0.0434

AC:

6612

AN:

152268

Hom.:

382

Cov.:

AF XY:

0.0454

AC XY:

3382

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00955

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0209

Gnomad4 FIN

AF:

0.0576

Gnomad4 NFE

AF:

0.0387

Gnomad4 OTH

AF:

0.0492

Alfa

AF:

0.0430

Hom.:

Bravo

AF:

0.0518

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.26

DANN

Benign

0.29

BranchPoint Hunter

3.0

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

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