chr2-48646651-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006872.5(GTF2A1L):ā€‹c.587A>Cā€‹(p.Gln196Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 152,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)

Consequence

GTF2A1L
NM_006872.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14732924).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GTF2A1LNM_006872.5 linkuse as main transcriptc.587A>C p.Gln196Pro missense_variant 6/9 ENST00000403751.8
STON1-GTF2A1LNM_001198593.2 linkuse as main transcriptc.2699A>C p.Gln900Pro missense_variant 8/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GTF2A1LENST00000403751.8 linkuse as main transcriptc.587A>C p.Gln196Pro missense_variant 6/91 NM_006872.5 P1Q9UNN4-1
GTF2A1LENST00000430487.6 linkuse as main transcriptc.485A>C p.Gln162Pro missense_variant 5/82 Q9UNN4-2
GTF2A1LENST00000437125.5 linkuse as main transcriptc.614A>C p.Gln205Pro missense_variant 6/64
GTF2A1LENST00000448460.5 linkuse as main transcriptc.485A>C p.Gln162Pro missense_variant 5/54

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000642

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 GeneticsJan 19, 2024The c.587A>C (p.Q196P) alteration is located in exon 6 (coding exon 6) of the GTF2A1L gene. This alteration results from a A to C substitution at nucleotide position 587, causing the glutamine (Q) at amino acid position 196 to be replaced by a proline (P). 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
0.082
BayesDel_addAF
Benign
-0.082
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
17
DANN
Benign
0.90
DEOGEN2
Benign
0.083
.;.;.;.;.;.;.;T
Eigen
Benign
-0.74
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.66
.;T;T;T;T;T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.15
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.2
.;.;.;.;.;.;.;M
MutationTaster
Benign
1.0
N;N;N;N;N;N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.2
N;N;N;N;D;N;N;N
REVEL
Benign
0.12
Sift
Benign
0.19
T;T;T;T;D;T;T;D
Sift4G
Benign
0.30
T;T;T;T;T;T;T;T
Polyphen
0.0040
B;.;B;.;.;.;B;B
Vest4
0.42
MutPred
0.63
Gain of catalytic residue at Q900 (P = 0.0038);Gain of catalytic residue at Q900 (P = 0.0038);Gain of catalytic residue at Q900 (P = 0.0038);.;.;.;.;.;
MVP
0.12
MPC
0.012, 0.0071
ClinPred
0.28
T
GERP RS
1.4
Varity_R
0.15
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs1677527254; hg19: chr2-48873790; API