1-109066134-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_005645.4(TAF13):​c.204+1G>T variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.000000688 in 1,452,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TAF13
NM_005645.4 splice_donor, intron

Scores

5
1
1
Splicing: ADA: 1.000
2

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 5.63
Variant links:
Genes affected
TAF13 (HGNC:11546): (TATA-box binding protein associated factor 13) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes a small subunit associated with a subset of TFIID complexes. This subunit interacts with TBP and with two other small subunits of TFIID, TAF10 and TAF11. There is a pseudogene located on chromosome 6. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-109066134-C-A is Pathogenic according to our data. Variant chr1-109066134-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1299252.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TAF13NM_005645.4 linkuse as main transcriptc.204+1G>T splice_donor_variant, intron_variant ENST00000338366.6 NP_005636.1 Q15543A0A024R089

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TAF13ENST00000338366.6 linkuse as main transcriptc.204+1G>T splice_donor_variant, intron_variant 1 NM_005645.4 ENSP00000355051.4 Q15543
TAF13ENST00000692048.1 linkuse as main transcriptc.204+1G>T splice_donor_variant, intron_variant ENSP00000508876.1 A0A8I5KR19
TAF13ENST00000461096.7 linkuse as main transcriptc.90+1G>T splice_donor_variant, intron_variant 5 ENSP00000433883.2 A0A8J9AJQ9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1452680
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
722816
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Intellectual disability, autosomal recessive 60 Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingBreda Genetics srlJan 14, 2021The variant c.204+1G>T in the TAF13 gene affects the donor splice site of intron 3 and is therefore highly likely to impact the splicing process by causing the retention of the following intron and the formation of an aberrant mRNA, which is unlikely to be exported and translated into protein. This variant has not been reported in dbSNP, gnomAD, 1000 Genomes Project or ClinVar. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.44
D
BayesDel_noAF
Pathogenic
0.39
CADD
Pathogenic
32
DANN
Uncertain
1.0
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.99
FATHMM_MKL
Pathogenic
0.99
D
GERP RS
5.5

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.94
SpliceAI score (max)
1.0
Details are displayed if max score is > 0.2
DS_DL_spliceai
1.0
Position offset: 1

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: chr1-109608756; API