NM_207118.3:c.36-5536C>A

Variant names:

• chr6-158186441-C-A
• rs4560672
• NM_207118.3:c.36-5536C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207118.3(GTF2H5):​c.36-5536C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,212 control chromosomes in the GnomAD database, including 6,016 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (6016 hom., cov: 33)
• Consequence: GTF2H5 NM_207118.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.31
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• trichothiodystrophy 3, photosensitive

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• trichothiodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207118.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2H5	NM_207118.3	MANE Select	c.36-5536C>A		intron	N/A	NP_997001.1	Q6ZYL4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2H5	ENST00000607778.2	TSL:1 MANE Select	c.36-5536C>A		intron	N/A	ENSP00000476100.1	Q6ZYL4
	GTF2H5	ENST00000889639.1		c.153-5536C>A		intron	N/A	ENSP00000559698.1
	GTF2H5	ENST00000689809.1		c.36-5536C>A		intron	N/A	ENSP00000510752.1	Q6ZYL4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33889 AN: 152094 Hom.: 6003 Cov.: 33

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0882

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.181

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.223 AC: 33940 AN: 152212 Hom.: 6016 Cov.: 33 AF XY: 0.217 AC XY: 16146 AN XY: 74430

African (AFR) AF: 0.493 AC: 20435 AN: 41484

American (AMR) AF: 0.116 AC: 1774 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 491 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5190

South Asian (SAS) AF: 0.115 AC: 556 AN: 4824

European-Finnish (FIN) AF: 0.0882 AC: 935 AN: 10606

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9246 AN: 68024

Other (OTH) AF: 0.181 AC: 382 AN: 2114

Alfa AF: 0.182 Hom.: 873

Bravo AF: 0.235

Asia WGS AF: 0.0810 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.033
DANN	Benign	0.20
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4560672; hg19: chr6-158607473; COSMIC: COSV74156315;