1-109064662-C-G

Variant names:

• chr1-109064662-C-G
• rs778604052
• NM_005645.4:c.236G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP2

The NM_005645.4(TAF13):​c.236G>C​(p.Gly79Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,384,952 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G79V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TAF13 NM_005645.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.38
• Publications: 0 publications found

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]

TAF13 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 60

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.2612 (below the threshold of 3.09). Trascript score misZ: 1.0066 (below the threshold of 3.09). GenCC associations: The gene is linked to intellectual disability, autosomal recessive 60, autosomal recessive primary microcephaly.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005645.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF13	NM_005645.4	MANE Select	c.236G>C	p.Gly79Ala	missense	Exon 4 of 4	NP_005636.1	Q15543

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF13	ENST00000338366.6	TSL:1 MANE Select	c.236G>C	p.Gly79Ala	missense	Exon 4 of 4	ENSP00000355051.4	Q15543
	TAF13	ENST00000692048.1		c.358G>C	p.Val120Leu	missense	Exon 5 of 5	ENSP00000508876.1	A0A8I5KR19
	TAF13	ENST00000461096.7	TSL:5	c.122G>C	p.Gly41Ala	missense	Exon 4 of 4	ENSP00000433883.2	A0A8J9AJQ9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1384952 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 687464

African (AFR) AF: 0.00 AC: 0 AN: 30480

American (AMR) AF: 0.00 AC: 0 AN: 33420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24194

East Asian (EAS) AF: 0.00 AC: 0 AN: 35936

South Asian (SAS) AF: 0.00 AC: 0 AN: 71996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5504

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1075378

Other (OTH) AF: 0.00 AC: 0 AN: 56736

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0093	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.33
Sift	Benign	0.042	D
Sift4G	Benign	0.067	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.55		Gain of helix (P = 0.0425)
MVP		0.61
MPC		2.1
ClinPred		1.0	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.64
gMVP		0.79
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs778604052; hg19: chr1-109607284;