10-91942424-C-T

Variant names:

• chr10-91942424-C-T
• rs765617555
• NM_003972.3:c.256C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003972.3(BTAF1):​c.256C>T​(p.Pro86Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000825 in 1,455,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. P86A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: BTAF1 NM_003972.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431
• Publications: 0 publications found

Genes affected

BTAF1 (HGNC:17307): (B-TFIID TATA-box binding protein associated factor 1) This gene encodes a TAF (TATA box-binding protein-associated factor), which associates with TBP (TATA box-binding protein) to form the B-TFIID complex that is required for transcription initiation of genes by RNA polymerase II. This TAF has DNA-dependent ATPase activity, which drives the dissociation of TBP from DNA, freeing the TBP to associate with other TATA boxes or TATA-less promoters. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03880331).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003972.3. 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
	BTAF1	NM_003972.3	MANE Select	c.256C>T	p.Pro86Ser	missense splice_region	Exon 4 of 38	NP_003963.1	Q2M1V9
	BTAF1	NR_165090.1		n.563C>T		splice_region non_coding_transcript_exon	Exon 4 of 37
	BTAF1	NR_165091.1		n.563C>T		splice_region non_coding_transcript_exon	Exon 4 of 39

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTAF1	ENST00000265990.12	TSL:1 MANE Select	c.256C>T	p.Pro86Ser	missense splice_region	Exon 4 of 38	ENSP00000265990.6	O14981-1
	BTAF1	ENST00000928671.1		c.256C>T	p.Pro86Ser	missense splice_region	Exon 4 of 37	ENSP00000598730.1
	BTAF1	ENST00000928670.1		c.256C>T	p.Pro86Ser	missense splice_region	Exon 4 of 37	ENSP00000598729.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000825 AC: 12 AN: 1455412 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 724018

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 44490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25964

East Asian (EAS) AF: 0.00 AC: 0 AN: 39188

South Asian (SAS) AF: 0.00 AC: 0 AN: 86120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1107804

Other (OTH) AF: 0.00 AC: 0 AN: 59986

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.87
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.43
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.23
Sift	Benign	0.86	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.089
MutPred		0.17		Gain of phosphorylation at P86 (P = 0.0056)
MVP		0.29
MPC		0.49
ClinPred		0.035	T
GERP RS		0.21
Varity_R		0.022
gMVP		0.094
Mutation Taster		=84/16	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: rs765617555; hg19: chr10-93702181;