10-91942479-A-G

Position:

• chr10-91942479-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003972.3(BTAF1):​c.311A>G​(p.Asp104Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: BTAF1 NM_003972.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3673938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTAF1	NM_003972.3	c.311A>G	p.Asp104Gly	missense_variant	4/38	ENST00000265990.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTAF1	ENST00000265990.12	c.311A>G	p.Asp104Gly	missense_variant	4/38	1	NM_003972.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.311A>G (p.D104G) alteration is located in exon 4 (coding exon 4) of the BTAF1 gene. This alteration results from a A to G substitution at nucleotide position 311, causing the aspartic acid (D) at amino acid position 104 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D;.
Eigen	Benign	0.013
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Uncertain	-0.082	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.3	D;.
REVEL	Uncertain	0.32
Sift	Benign	0.19	T;.
Sift4G	Benign	0.19	T;T
Polyphen		0.0070	B;.
Vest4		0.53
MutPred		0.42		Loss of stability (P = 0.0088);Loss of stability (P = 0.0088);
MVP		0.75
MPC		0.64
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.28
gMVP		0.33

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-93702236;