16-84179001-C-G

Variant names:

• chr16-84179001-C-G
• rs1392786026
• NM_001243156.2:c.2472G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001243156.2(TAF1C):​c.2472G>C​(p.Gln824His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,458,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TAF1C NM_001243156.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.286

Genes affected

TAF1C (HGNC:11534): (TATA-box binding protein associated factor, RNA polymerase I subunit C) Initiation of transcription by RNA polymerase I requires the formation of a complex composed of the TATA-binding protein (TBP) and three TBP-associated factors (TAFs) specific for RNA polymerase I. This complex, known as SL1, binds to the core promoter of ribosomal RNA genes to position the polymerase properly and acts as a channel for regulatory signals. This gene encodes the largest SL1-specific TAF. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2011]

DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10904801).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1C	NM_001243156.2	c.2472G>C	p.Gln824His	missense_variant	Exon 15 of 15	ENST00000566732.6	NP_001230085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1C	ENST00000566732.6	c.2472G>C	p.Gln824His	missense_variant	Exon 15 of 15	2	NM_001243156.2	ENSP00000455933.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247234 AF XY: 0.00000746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1458346 Hom.: 0 Cov.: 55 AF XY: 0.00000413 AC XY: 3 AN XY: 725560

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.0000200 AC: 1 AN: 50074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111906

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2550G>C (p.Q850H) alteration is located in exon 14 (coding exon 13) of the TAF1C gene. This alteration results from a G to C substitution at nucleotide position 2550, causing the glutamine (Q) at amino acid position 850 to be replaced by a histidine (H). 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	0.19
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0072	.;.;T;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.52	T;T;T;T;.
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;.;L;.;.
PhyloP100		-0.29
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.5	.;N;N;N;N
REVEL	Benign	0.081
Sift	Uncertain	0.019	.;D;D;D;D
Sift4G	Uncertain	0.036	D;D;D;D;D
Polyphen		0.91	.;P;P;P;.
Vest4		0.17
MutPred		0.23		.;.;Gain of catalytic residue at Q850 (P = 0.0767);.;.;
MVP		0.23
ClinPred		0.46	T
GERP RS		0.31
Varity_R		0.055
gMVP		0.15
Mutation Taster		=98/2	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

Publications

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Other links and lift over

dbSNP: rs1392786026; hg19: chr16-84212607;