rs753328893

Variant names:

• chr19-6380456-C-A
• rs753328893
• NM_002096.3:c.1379G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-6380456-C-A
• chr19-6380456-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002096.3(GTF2F1):​c.1379G>T​(p.Arg460Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R460C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GTF2F1 NM_002096.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.34

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.831

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2F1	NM_002096.3	c.1379G>T	p.Arg460Leu	missense_variant	Exon 13 of 13	ENST00000394456.10	NP_002087.2
GTF2F1	XM_047438710.1	c.1406G>T	p.Arg469Leu	missense_variant	Exon 12 of 12		XP_047294666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2F1	ENST00000394456.10	c.1379G>T	p.Arg460Leu	missense_variant	Exon 13 of 13	1	NM_002096.3	ENSP00000377969.3
GTF2F1	ENST00000593678.5	c.1127G>T	p.Arg376Leu	missense_variant	Exon 10 of 10	2		ENSP00000469091.1
GTF2F1	ENST00000594213.5	n.736G>T		non_coding_transcript_exon_variant	Exon 6 of 6	3
GTF2F1	ENST00000594965.1	n.697G>T		non_coding_transcript_exon_variant	Exon 6 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-4.9	D;.
REVEL	Benign	0.26
Sift	Uncertain	0.0030	D;.
Sift4G	Uncertain	0.019	D;D
Polyphen		0.10	B;.
Vest4		0.69
MutPred		0.75		Loss of MoRF binding (P = 0.0214);.;
MVP		0.63
MPC		1.0
ClinPred		0.99	D
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.78
gMVP		0.88

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: rs753328893; hg19: chr19-6380467;