1-109075045-T-A

Variant names:

• chr1-109075045-T-A
• rs1664157339
• NM_005645.4:c.48A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_005645.4(TAF13):​c.48A>T​(p.Glu16Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAF13 NM_005645.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.810
• 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, MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 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.
• BP4: Computational evidence support a benign effect (MetaRNN=0.07896656).

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.48A>T	p.Glu16Asp	missense	Exon 2 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.48A>T	p.Glu16Asp	missense	Exon 2 of 4	ENSP00000355051.4	Q15543
	TAF13	ENST00000692048.1		c.48A>T	p.Glu16Asp	missense	Exon 2 of 5	ENSP00000508876.1	A0A8I5KR19
	TAF13	ENST00000461096.7	TSL:5	c.-67A>T		5_prime_UTR	Exon 2 of 4	ENSP00000433883.2	A0A8J9AJQ9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.051
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.11	N
PhyloP100		0.81
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.099
Sift	Benign	0.61	T
Sift4G	Benign	0.49	T
Polyphen		0.27	B
Vest4		0.27
MutPred		0.10		Gain of loop (P = 0.0435)
MVP		0.30
MPC		0.85
ClinPred		0.44	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.14
gMVP		0.056
Mutation Taster		=94/6	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: rs1664157339; hg19: chr1-109617667;