12-123650255-C-T

Position:

• chr12-123650255-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001516.5(GTF2H3):​c.365-739C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 152,260 control chromosomes in the GnomAD database, including 265 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 0.052 (265 hom., cov: 32)
  • Exomes 𝑓: 0.040 (0 hom.)
• Consequence: GTF2H3 NM_001516.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

Genes affected

GTF2H3 (HGNC:4657): (general transcription factor IIH subunit 3) This gene encodes a member of the TFB4 family. The encoded protein is a subunit of the core-TFIIH basal transcription factor and localizes to the nucleus. The encoded protein is involved in RNA transcription by RNA polymerase II and nucleotide excision repair and associates with the Cdk-activating kinase complex. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 14. [provided by RefSeq, Dec 2012]

ENSG00000279953 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2H3	NM_001516.5	c.365-739C>T		intron_variant		ENST00000543341.7	NP_001507.2
GTF2H3	NM_001271867.2	c.242-739C>T		intron_variant			NP_001258796.1
GTF2H3	NM_001271866.2	c.365-739C>T		intron_variant			NP_001258795.1
GTF2H3	NM_001271868.2	c.-74-739C>T		intron_variant			NP_001258797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2H3	ENST00000543341.7	c.365-739C>T		intron_variant		1	NM_001516.5	ENSP00000445162.1

Frequencies

GnomAD3 genomes AF: 0.0518 AC: 7880 AN: 152092 Hom.: 265 Cov.: 32

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0550

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.0427

GnomAD4 exome AF: 0.0400 AC: 2 AN: 50 Hom.: 0 Cov.: 0 AF XY: 0.0238 AC XY: 1 AN XY: 42

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0556

GnomAD4 genome AF: 0.0517 AC: 7876 AN: 152210 Hom.: 265 Cov.: 32 AF XY: 0.0483 AC XY: 3593 AN XY: 74404

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.0549

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0345

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.0422

Alfa AF: 0.0682 Hom.: 546

Bravo AF: 0.0528

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs11572966; hg19: chr12-124134802;