16-84177908-T-C

Variant names:

• chr16-84177908-T-C
• rs4150186
• NM_001243156.2:c.*1033A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001243156.2(TAF1C):​c.*1033A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,331,770 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (12 hom.)
• Consequence: TAF1C NM_001243156.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.183
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-84177908-T-C is Benign according to our data. Variant chr16-84177908-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 320784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00591 (900/152288) while in subpopulation AFR AF = 0.0206 (857/41550). AF 95% confidence interval is 0.0195. There are 11 homozygotes in GnomAd4. There are 427 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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.*1033A>G		3_prime_UTR	Exon 15 of 15	NP_001230085.2	Q15572-6
	DNAAF1	NM_178452.6	MANE Select	c.*67T>C		3_prime_UTR	Exon 12 of 12	NP_848547.4
	TAF1C	NM_005679.4		c.*1033A>G		3_prime_UTR	Exon 14 of 14	NP_005670.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1C	ENST00000566732.6	TSL:2 MANE Select	c.*1033A>G		3_prime_UTR	Exon 15 of 15	ENSP00000455933.1	Q15572-6
	DNAAF1	ENST00000378553.10	TSL:1 MANE Select	c.*67T>C		3_prime_UTR	Exon 12 of 12	ENSP00000367815.5	Q8NEP3-1
	TAF1C	ENST00000341690.10	TSL:1	c.*1033A>G		3_prime_UTR	Exon 15 of 15	ENSP00000345305.6	Q15572-2

Frequencies

GnomAD3 genomes AF: 0.00584 AC: 889 AN: 152170 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.000667 AC: 787 AN: 1179482 Hom.: 12 Cov.: 16 AF XY: 0.000583 AC XY: 350 AN XY: 600114

African (AFR) AF: 0.0220 AC: 611 AN: 27788

American (AMR) AF: 0.000798 AC: 35 AN: 43854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24180

East Asian (EAS) AF: 0.00 AC: 0 AN: 38200

South Asian (SAS) AF: 0.0000871 AC: 7 AN: 80392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52108

Middle Eastern (MID) AF: 0.00138 AC: 7 AN: 5074

European-Non Finnish (NFE) AF: 0.0000152 AC: 13 AN: 857012

Other (OTH) AF: 0.00224 AC: 114 AN: 50874

GnomAD4 genome AF: 0.00591 AC: 900 AN: 152288 Hom.: 11 Cov.: 32 AF XY: 0.00573 AC XY: 427 AN XY: 74464

African (AFR) AF: 0.0206 AC: 857 AN: 41550

American (AMR) AF: 0.00170 AC: 26 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00151 Hom.: 1

Bravo AF: 0.00670

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary ciliary dyskinesia 13 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.49
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4150186; hg19: chr16-84211514; COSMIC: COSV107447561; COSMIC: COSV107447561;