13-45120684-C-T

Variant names:

• chr13-45120684-C-T
• NM_004128.3:c.29C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004128.3(GTF2F2):​c.29C>T​(p.Thr10Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000142 in 1,409,362 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GTF2F2 NM_004128.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85
• Publications: 0 publications found

Genes affected

GTF2F2 (HGNC:4653): (general transcription factor IIF subunit 2) Predicted to enable RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in microtubule cytoskeleton and nucleoplasm. Part of transcription preinitiation complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39259925).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004128.3. 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
	GTF2F2	NM_004128.3	MANE Select	c.29C>T	p.Thr10Ile	missense	Exon 1 of 8	NP_004119.1	P13984

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2F2	ENST00000340473.8	TSL:1 MANE Select	c.29C>T	p.Thr10Ile	missense	Exon 1 of 8	ENSP00000340823.6	P13984
	GTF2F2	ENST00000883031.1		c.29C>T	p.Thr10Ile	missense	Exon 1 of 9	ENSP00000553090.1
	GTF2F2	ENST00000912524.1		c.29C>T	p.Thr10Ile	missense	Exon 1 of 9	ENSP00000582583.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1409362 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 695968

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32460

American (AMR) AF: 0.00 AC: 0 AN: 36776

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25220

East Asian (EAS) AF: 0.00 AC: 0 AN: 37154

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083966

Other (OTH) AF: 0.0000171 AC: 1 AN: 58418

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.9
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.045	D
Polyphen		0.83	P
Vest4		0.42
MutPred		0.54		Gain of catalytic residue at N15 (P = 0.0023)
MVP		0.67
MPC		1.0
ClinPred		0.98	D
GERP RS		5.2
PromoterAI		0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.71
gMVP		0.48
Mutation Taster		=47/53	disease causing

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

hg19: chr13-45694819;