chr2-48646675-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006872.5(GTF2A1L):​c.611C>T​(p.Pro204Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000429 in 1,614,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00044 ( 0 hom. )

Consequence

GTF2A1L
NM_006872.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.539
Variant links:
Genes affected
GTF2A1L (HGNC:30727): (general transcription factor IIA subunit 1 like) The assembly and stability of the RNA polymerase II transcription pre-initiation complex on a eukaryotic core promoter involve the effects of transcription factor IIA (TFIIA) on the interaction between TATA-binding protein (TBP) and DNA. This gene encodes a germ cell-specific counterpart of the large (alpha/beta) subunit of general transcription factor TFIIA that is able to stabilize the binding of TBP to DNA and may be uniquely important to testis biology. Alternative splicing for this locus has been observed and two variants, encoding distinct isoforms, have been identified. Co-transcription of this gene and the neighboring upstream gene generates a rare transcript (SALF), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Mar 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.00872919).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GTF2A1LNM_006872.5 linkuse as main transcriptc.611C>T p.Pro204Leu missense_variant 6/9 ENST00000403751.8
STON1-GTF2A1LNM_001198593.2 linkuse as main transcriptc.2723C>T p.Pro908Leu missense_variant 8/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GTF2A1LENST00000403751.8 linkuse as main transcriptc.611C>T p.Pro204Leu missense_variant 6/91 NM_006872.5 P1Q9UNN4-1
GTF2A1LENST00000430487.6 linkuse as main transcriptc.509C>T p.Pro170Leu missense_variant 5/82 Q9UNN4-2
GTF2A1LENST00000437125.5 linkuse as main transcriptc.638C>T p.Pro213Leu missense_variant 6/64
GTF2A1LENST00000448460.5 linkuse as main transcript downstream_gene_variant 4

Frequencies

GnomAD3 genomes
AF:
0.000342
AC:
52
AN:
152132
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00461
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000397
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000478
AC:
119
AN:
248878
Hom.:
0
AF XY:
0.000445
AC XY:
60
AN XY:
134710
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00437
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000548
Gnomad OTH exome
AF:
0.000982
GnomAD4 exome
AF:
0.000438
AC:
640
AN:
1461856
Hom.:
0
Cov.:
33
AF XY:
0.000451
AC XY:
328
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00406
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000197
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000406
Gnomad4 OTH exome
AF:
0.000662
GnomAD4 genome
AF:
0.000342
AC:
52
AN:
152250
Hom.:
0
Cov.:
32
AF XY:
0.000269
AC XY:
20
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00461
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000397
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.000695
Hom.:
0
Bravo
AF:
0.000385
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000581
AC:
5
ExAC
AF:
0.000379
AC:
46
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000927
EpiControl
AF:
0.00101

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 03, 2021The c.611C>T (p.P204L) alteration is located in exon 6 (coding exon 6) of the GTF2A1L gene. This alteration results from a C to T substitution at nucleotide position 611, causing the proline (P) at amino acid position 204 to be replaced by a leucine (L). 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
Benign
0.067
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
4.8
DANN
Benign
0.83
DEOGEN2
Benign
0.060
.;.;.;.;.;.;T
Eigen
Benign
-0.88
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.73
.;T;T;T;T;T;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.0087
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
.;.;.;.;.;.;M
MutationTaster
Benign
1.0
N;N;N;N;N;N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.1
N;N;N;N;N;N;N
REVEL
Benign
0.094
Sift
Benign
0.079
T;T;T;T;D;D;D
Sift4G
Benign
0.28
T;T;T;T;T;T;T
Polyphen
0.015
B;.;B;.;.;P;B
Vest4
0.072
MVP
0.092
MPC
0.0036, 0.0064
ClinPred
0.011
T
GERP RS
1.5
Varity_R
0.033
gMVP
0.17

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: rs200588064; hg19: chr2-48873814; API