10-91942424-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003972.3(BTAF1):​c.256C>G​(p.Pro86Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,607,228 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: BTAF1 NM_003972.3 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04812959).

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>G	p.Pro86Ala	missense splice_region	Exon 4 of 38	NP_003963.1	Q2M1V9
	BTAF1	NR_165090.1		n.563C>G		splice_region non_coding_transcript_exon	Exon 4 of 37
	BTAF1	NR_165091.1		n.563C>G		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>G	p.Pro86Ala	missense splice_region	Exon 4 of 38	ENSP00000265990.6	O14981-1
	BTAF1	ENST00000928671.1		c.256C>G	p.Pro86Ala	missense splice_region	Exon 4 of 37	ENSP00000598730.1
	BTAF1	ENST00000928670.1		c.256C>G	p.Pro86Ala	missense splice_region	Exon 4 of 37	ENSP00000598729.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151814 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1455414 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724020

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: 0.00000361 AC: 4 AN: 1107806

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

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151814 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74128

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41358

American (AMR) AF: 0.00 AC: 0 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	0.055
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.43
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.24
Sift	Benign	0.77	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.13		Loss of glycosylation at P86 (P = 0.0335)
MVP		0.35
MPC		0.47
ClinPred		0.030	T
GERP RS		0.21
Varity_R		0.022
gMVP		0.092
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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;