16-84178112-C-T

Position:

• chr16-84178112-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001243156.2(TAF1C):​c.*829G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 435,124 control chromosomes in the GnomAD database, including 4,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1982 hom., cov: 32)
  • Exomes 𝑓: 0.12 (2530 hom.)
• Consequence: TAF1C NM_001243156.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.03

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-84178112-C-T is Benign according to our data. Variant chr16-84178112-C-T is described in ClinVar as [Benign]. Clinvar id is 1237217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF1C	NM_001243156.2	c.*829G>A		3_prime_UTR_variant	15/15	ENST00000566732.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF1C	ENST00000566732.6	c.*829G>A		3_prime_UTR_variant	15/15	2	NM_001243156.2	P2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22101 AN: 151808 Hom.: 1976 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0924

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.121 AC: 34395 AN: 283198 Hom.: 2530 Cov.: 0 AF XY: 0.129 AC XY: 19867 AN XY: 153904

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.0773

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.0916

Gnomad4 NFE exome AF: 0.0926

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.146 AC: 22134 AN: 151926 Hom.: 1982 Cov.: 32 AF XY: 0.145 AC XY: 10751 AN XY: 74248

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.0813

Gnomad4 NFE AF: 0.0924

Gnomad4 OTH AF: 0.156

Alfa AF: 0.108 Hom.: 1462

Bravo AF: 0.149

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.51

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

LitVar

Other links and lift over

dbSNP: rs1056616; hg19: chr16-84211718;