1-109066143-T-C

Position:

• chr1-109066143-T-C

Variant summary

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

The NM_005645.4(TAF13):​c.196A>G​(p.Thr66Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000357 in 1,455,602 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: TAF13 NM_005645.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.44

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/exons	MANE	Protein	UniProt
TAF13	NM_005645.4	c.196A>G	p.Thr66Ala	missense_variant	3/4	ENST00000338366.6	NP_005636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF13	ENST00000338366.6	c.196A>G	p.Thr66Ala	missense_variant	3/4	1	NM_005645.4	ENSP00000355051.4
TAF13	ENST00000692048.1	c.196A>G	p.Thr66Ala	missense_variant	3/5			ENSP00000508876.1
TAF13	ENST00000461096.7	c.82A>G	p.Thr28Ala	missense_variant	3/4	5		ENSP00000433883.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000357 AC: 52 AN: 1455602 Hom.: 0 Cov.: 29 AF XY: 0.0000387 AC XY: 28 AN XY: 724122

Gnomad4 AFR exome AF: 0.0000302

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: 0.0000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.196A>G (p.T66A) alteration is located in exon 3 (coding exon 3) of the TAF13 gene. This alteration results from a A to G substitution at nucleotide position 196, causing the threonine (T) at amino acid position 66 to be replaced by an alanine (A). 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	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0044	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.28
Sift	Benign	0.13	T
Sift4G	Benign	0.77	T
Polyphen		0.037	B
Vest4		0.94
MutPred		0.44		Loss of ubiquitination at K71 (P = 0.1322);
MVP		0.29
MPC		1.0
ClinPred		0.91	D
GERP RS		5.7
Varity_R		0.30
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-109608765;