6-158168365-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_207118.3(GTF2H5):c.-65C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00959 in 152,358 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GTF2H5
NM_207118.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.505

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:

SERAC1 (HGNC:21061): (serine active site containing 1) The protein encoded by this gene is a phosphatidylglycerol remodeling protein found at the interface of mitochondria and endoplasmic reticula, where it mediates phospholipid exchange. The encoded protein plays a major role in mitochondrial function and intracellular cholesterol trafficking. Defects in this gene are a cause of 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL). Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Aug 2012]

SERAC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 6-158168365-C-T is Benign according to our data. Variant chr6-158168365-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1254217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00959 (1461/152358) while in subpopulation AMR AF= 0.0152 (232/15304). AF 95% confidence interval is 0.0142. There are 8 homozygotes in gnomad4. There are 635 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GTF2H5	NM_207118.3 link	c.-65C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	ENST00000607778.2	NP_997001.1	Q6ZYL4
GTF2H5	NM_207118.3 link	c.-65C>T	5_prime_UTR_variant	Exon 1 of 3	ENST00000607778.2	NP_997001.1	Q6ZYL4
SERAC1	NM_032861.4 link	c.-227G>A	upstream_gene_variant		ENST00000647468.2	NP_116250.3	Q96JX3-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GTF2H5	ENST00000607778 link	c.-65C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	1	NM_207118.3	ENSP00000476100.1	Q6ZYL4
GTF2H5	ENST00000607778 link	c.-65C>T	5_prime_UTR_variant	Exon 1 of 3	1	NM_207118.3	ENSP00000476100.1	Q6ZYL4
SERAC1	ENST00000647468.2 link	c.-227G>A	upstream_gene_variant			NM_032861.4	ENSP00000496731.1	Q96JX3-1

Frequencies

GnomAD3 genomes

AF:

0.00960

AC:

1462

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00285

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0152

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0149

Gnomad OTH

AF:

0.0143

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

114

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00959

AC:

1461

AN:

152358

Hom.:

Cov.:

AF XY:

0.00852

AC XY:

635

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00286

Gnomad4 AMR

AF:

0.0152

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.0149

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00963

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 26, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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