1-109074995-G-GA

Variant names:

• chr1-109074995-G-GA
• rs778508331
• NM_005645.4:c.97dupT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005645.4(TAF13):​c.97dupT​(p.Ser33PhefsTer2) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000307 in 1,595,252 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: TAF13 NM_005645.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF13	NM_005645.4	c.97dupT	p.Ser33PhefsTer2	frameshift_variant	Exon 2 of 4	ENST00000338366.6	NP_005636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF13	ENST00000338366.6	c.97dupT	p.Ser33PhefsTer2	frameshift_variant	Exon 2 of 4	1	NM_005645.4	ENSP00000355051.4
TAF13	ENST00000692048.1	c.97dupT	p.Ser33PhefsTer2	frameshift_variant	Exon 2 of 5			ENSP00000508876.1
TAF13	ENST00000461096.7	c.-18dupT		5_prime_UTR_variant	Exon 2 of 4	5		ENSP00000433883.2

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152052 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

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: 0.00144

GnomAD3 exomes AF: 0.0000342 AC: 8 AN: 233776 Hom.: 0 AF XY: 0.00000791 AC XY: 1 AN XY: 126460

Gnomad AFR exome AF: 0.000313

Gnomad AMR exome AF: 0.000103

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000187 AC: 27 AN: 1443082 Hom.: 0 Cov.: 29 AF XY: 0.0000139 AC XY: 10 AN XY: 717770

Gnomad4 AFR exome AF: 0.000527

Gnomad4 AMR exome AF: 0.000155

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: 0.00

Gnomad4 OTH exome AF: 0.0000671

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74394

Gnomad4 AFR AF: 0.000361

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: 0.00142

Bravo AF: 0.000246

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 09, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: TAF13 c.97dupT (p.Ser33PhefsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, however the molecular mechanism of disease attributed to TAF13 is currently unknown. The variant allele was found at a frequency of 3.4e-05 in 233776 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.97dupT in individuals affected with Intellectual Disability, Autosomal Recessive 60 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs778508331; hg19: chr1-109617617;