X-78138072-C-G

Variant names:

• chrX-78138072-C-G
• rs782268006
• NM_015975.5:c.160G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_015975.5(TAF9B):​c.160G>C​(p.Ala54Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TAF9B NM_015975.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.44
• Publications: 0 publications found

Genes affected

TAF9B (HGNC:17306): (TATA-box binding protein associated factor 9b) 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 protein that is similar to one of the small subunits of TFIID, TBP-associated factor 9, and is also a subunit of TFIID. TAF9 and TAF9b share some functions but also have distinct roles in the transcriptional regulatory process. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.973

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015975.5. 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
	TAF9B	NM_015975.5	MANE Select	c.160G>C	p.Ala54Pro	missense	Exon 3 of 7	NP_057059.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF9B	ENST00000341864.6	TSL:1 MANE Select	c.160G>C	p.Ala54Pro	missense	Exon 3 of 7	ENSP00000339917.5	Q9HBM6
	TAF9B	ENST00000888659.1		c.160G>C	p.Ala54Pro	missense	Exon 3 of 6	ENSP00000558718.1
	TAF9B	ENST00000888658.1		c.160G>C	p.Ala54Pro	missense	Exon 3 of 6	ENSP00000558717.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.069	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	-0.055	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.4
PrimateAI	Pathogenic	0.80	D
PROVEAN	Pathogenic	-4.4	D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.91		Loss of helix (P = 0.0167)
MVP		0.89
MPC		0.60
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.97
gMVP		0.91
Mutation Taster		=69/31	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: rs782268006; hg19: chrX-77393569;