19-6380286-C-T

Variant names:

• chr19-6380286-C-T
• NM_002096.3:c.1549G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002096.3(GTF2F1):​c.1549G>A​(p.Glu517Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GTF2F1 NM_002096.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.28

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37350872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2F1	NM_002096.3	c.1549G>A	p.Glu517Lys	missense_variant	Exon 13 of 13	ENST00000394456.10	NP_002087.2
GTF2F1	XM_047438710.1	c.1576G>A	p.Glu526Lys	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.1549G>A	p.Glu517Lys	missense_variant	Exon 13 of 13	1	NM_002096.3	ENSP00000377969.3
GTF2F1	ENST00000593678.5	c.1297G>A	p.Glu433Lys	missense_variant	Exon 10 of 10	2		ENSP00000469091.1
GTF2F1	ENST00000594213.5	n.906G>A		non_coding_transcript_exon_variant	Exon 6 of 6	3
GTF2F1	ENST00000594965.1	n.*105G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1549G>A (p.E517K) alteration is located in exon 13 (coding exon 13) of the GTF2F1 gene. This alteration results from a G to A substitution at nucleotide position 1549, causing the glutamic acid (E) at amino acid position 517 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.082	T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.15	T;T
Polyphen		0.62	P;.
Vest4		0.17
MutPred		0.54		Gain of MoRF binding (P = 2e-04);.;
MVP		0.68
MPC		0.41
ClinPred		0.91	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.90
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-6380297;