NM_001243156.2:c.*829G>A

Variant names:

• chr16-84178112-C-T
• rs1056616
• NM_001243156.2:c.*829G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

DNAAF1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 13

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243156.2. 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
	TAF1C	NM_001243156.2	MANE Select	c.*829G>A		3_prime_UTR	Exon 15 of 15	NP_001230085.2	Q15572-6
	TAF1C	NM_005679.4		c.*829G>A		3_prime_UTR	Exon 14 of 14	NP_005670.4
	TAF1C	NM_139353.3		c.*829G>A		3_prime_UTR	Exon 15 of 15	NP_647610.3	Q15572-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1C	ENST00000566732.6	TSL:2 MANE Select	c.*829G>A		3_prime_UTR	Exon 15 of 15	ENSP00000455933.1	Q15572-6
	TAF1C	ENST00000341690.10	TSL:1	c.*829G>A		3_prime_UTR	Exon 15 of 15	ENSP00000345305.6	Q15572-2
	TAF1C	ENST00000567759.5	TSL:2	c.*829G>A		3_prime_UTR	Exon 14 of 14	ENSP00000455265.1	Q15572-1

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

African (AFR) AF: 0.234 AC: 1866 AN: 7970

American (AMR) AF: 0.0773 AC: 1153 AN: 14922

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 1133 AN: 7960

East Asian (EAS) AF: 0.204 AC: 2965 AN: 14516

South Asian (SAS) AF: 0.202 AC: 8900 AN: 43996

European-Finnish (FIN) AF: 0.0916 AC: 1256 AN: 13718

Middle Eastern (MID) AF: 0.131 AC: 171 AN: 1304

European-Non Finnish (NFE) AF: 0.0926 AC: 15171 AN: 163792

Other (OTH) AF: 0.119 AC: 1780 AN: 15020

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

African (AFR) AF: 0.249 AC: 10289 AN: 41342

American (AMR) AF: 0.108 AC: 1648 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3468

East Asian (EAS) AF: 0.213 AC: 1102 AN: 5164

South Asian (SAS) AF: 0.204 AC: 981 AN: 4798

European-Finnish (FIN) AF: 0.0813 AC: 858 AN: 10556

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0924 AC: 6284 AN: 68002

Other (OTH) AF: 0.156 AC: 329 AN: 2114

Alfa AF: 0.112 Hom.: 1995

Bravo AF: 0.149

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.51
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs1056616; hg19: chr16-84211718;