NM_002096.3:c.1027G>T

Variant names:

• chr19-6381187-C-A
• rs752299707
• NM_002096.3:c.1027G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002096.3(GTF2F1):​c.1027G>T​(p.Glu343*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000687 in 1,456,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GTF2F1 NM_002096.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.54
• Publications: 1 publications found

Genes affected

GTF2F1 (HGNC:4652): (general transcription factor IIF subunit 1) Enables several functions, including RNA polymerase II general transcription initiation factor activity; phosphatase activator activity; and promoter-specific chromatin binding activity. Involved in several processes, including positive regulation of transcription by RNA polymerase II; response to virus; and transcription initiation from RNA polymerase II promoter. Located in cell junction and nucleoplasm. Part of transcription factor TFIID complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002096.3. 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
	GTF2F1	NM_002096.3	MANE Select	c.1027G>T	p.Glu343*	stop_gained	Exon 10 of 13	NP_002087.2	P35269

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2F1	ENST00000394456.10	TSL:1 MANE Select	c.1027G>T	p.Glu343*	stop_gained	Exon 10 of 13	ENSP00000377969.3	P35269
	GTF2F1	ENST00000869875.1		c.1027G>T	p.Glu343*	stop_gained	Exon 10 of 13	ENSP00000539934.1
	GTF2F1	ENST00000933129.1		c.1027G>T	p.Glu343*	stop_gained	Exon 10 of 13	ENSP00000603188.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000416 AC: 1 AN: 240392 AF XY: 0.00000769

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000917

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456664 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 724258

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 43958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26014

East Asian (EAS) AF: 0.00 AC: 0 AN: 39544

South Asian (SAS) AF: 0.00 AC: 0 AN: 85432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110086

Other (OTH) AF: 0.00 AC: 0 AN: 60198

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	43
DANN	Uncertain	1.0
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.97	D
PhyloP100		5.5
Vest4		0.24
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=6/194	disease causing (fs/PTC)

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: rs752299707; hg19: chr19-6381198;