chr19-6380961-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002096.3(GTF2F1):​c.1174G>A​(p.Ala392Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,597,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

GTF2F1
NM_002096.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.77
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.039378136).
BP6
Variant 19-6380961-C-T is Benign according to our data. Variant chr19-6380961-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3283050.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GTF2F1NM_002096.3 linkc.1174G>A p.Ala392Thr missense_variant Exon 11 of 13 ENST00000394456.10 NP_002087.2 P35269
GTF2F1XM_047438710.1 linkc.1201G>A p.Ala401Thr missense_variant Exon 10 of 12 XP_047294666.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GTF2F1ENST00000394456.10 linkc.1174G>A p.Ala392Thr missense_variant Exon 11 of 13 1 NM_002096.3 ENSP00000377969.3 P35269
GTF2F1ENST00000593678.5 linkc.922G>A p.Ala308Thr missense_variant Exon 8 of 10 2 ENSP00000469091.1 M0QXD6
GTF2F1ENST00000594213.5 linkn.541G>A non_coding_transcript_exon_variant Exon 4 of 6 3
GTF2F1ENST00000594965.1 linkn.492G>A non_coding_transcript_exon_variant Exon 4 of 6 3

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152184
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000135
AC:
3
AN:
222482
Hom.:
0
AF XY:
0.0000165
AC XY:
2
AN XY:
120958
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000310
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000205
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000159
AC:
23
AN:
1445630
Hom.:
0
Cov.:
33
AF XY:
0.0000139
AC XY:
10
AN XY:
717806
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.0000233
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000145
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152184
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000831
ExAC
AF:
0.0000165
AC:
2
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Apr 06, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.058
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.011
DANN
Benign
0.82
DEOGEN2
Benign
0.053
T;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.60
T;T
M_CAP
Benign
0.0082
T
MetaRNN
Benign
0.039
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.20
N;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
0.51
N;.
REVEL
Benign
0.0080
Sift
Benign
0.51
T;.
Sift4G
Benign
0.58
T;T
Polyphen
0.0
B;.
Vest4
0.090
MVP
0.33
MPC
0.24
ClinPred
0.033
T
GERP RS
-6.3
Varity_R
0.011
gMVP
0.12

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777591705; hg19: chr19-6380972; API