X-78136987-G-T

Variant names:

• chrX-78136987-G-T
• rs371749672
• NM_015975.5:c.409C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_015975.5(TAF9B):​c.409C>A​(p.Pro137Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,070,702 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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. P137A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000013 (0 hom. 6 hem.)
• Consequence: TAF9B NM_015975.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52
• 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_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14936432).
• BS2: High Hemizygotes in GnomAdExome4 at 6 gene

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.409C>A	p.Pro137Thr	missense	Exon 5 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.409C>A	p.Pro137Thr	missense	Exon 5 of 7	ENSP00000339917.5	Q9HBM6
	TAF9B	ENST00000888659.1		c.409C>A	p.Pro137Thr	missense	Exon 5 of 6	ENSP00000558718.1
	TAF9B	ENST00000888658.1		c.274C>A	p.Pro92Thr	missense	Exon 4 of 6	ENSP00000558717.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.0000131 AC: 14 AN: 1070702 Hom.: 0 Cov.: 25 AF XY: 0.0000177 AC XY: 6 AN XY: 338794

African (AFR) AF: 0.00 AC: 0 AN: 25955

American (AMR) AF: 0.00 AC: 0 AN: 34513

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18870

East Asian (EAS) AF: 0.00 AC: 0 AN: 30046

South Asian (SAS) AF: 0.00 AC: 0 AN: 51523

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3949

European-Non Finnish (NFE) AF: 0.0000158 AC: 13 AN: 820819

Other (OTH) AF: 0.0000222 AC: 1 AN: 45011

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Benign	0.52
DEOGEN2	Benign	0.060	T
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
PhyloP100		2.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.10
Sift	Benign	0.40	T
Sift4G	Benign	0.69	T
Polyphen		0.95	P
Vest4		0.17
MutPred		0.23		Loss of glycosylation at P137 (P = 0.0692)
MVP		0.48
MPC		0.12
ClinPred		0.52	D
GERP RS		3.0
Varity_R		0.15
gMVP		0.45
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: rs371749672; hg19: chrX-77392484;