16-84177859-T-C

Variant names:

• chr16-84177859-T-C
• rs2288024
• NM_001243156.2:c.*1082A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001243156.2(TAF1C):​c.*1082A>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 0.038 in 1,586,902 control chromosomes in the GnomAD database, including 1,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (87 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1231 hom.)
• Consequence: TAF1C NM_001243156.2 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.92
• Publications: 6 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=-0.88).
• BP6: Variant 16-84177859-T-C is Benign according to our data. Variant chr16-84177859-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0307 (4677/152324) while in subpopulation NFE AF = 0.0439 (2986/68034). AF 95% confidence interval is 0.0426. There are 87 homozygotes in GnomAd4. There are 2313 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 87 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.*1082A>G		3_prime_UTR	Exon 15 of 15	NP_001230085.2	Q15572-6
	DNAAF1	NM_178452.6	MANE Select	c.*18T>C		3_prime_UTR	Exon 12 of 12	NP_848547.4
	TAF1C	NM_005679.4		c.*1082A>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.*1082A>G		3_prime_UTR	Exon 15 of 15	ENSP00000455933.1	Q15572-6
	DNAAF1	ENST00000378553.10	TSL:1 MANE Select	c.*18T>C		3_prime_UTR	Exon 12 of 12	ENSP00000367815.5	Q8NEP3-1
	TAF1C	ENST00000341690.10	TSL:1	c.*1082A>G		3_prime_UTR	Exon 15 of 15	ENSP00000345305.6	Q15572-2

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4681 AN: 152206 Hom.: 87 Cov.: 32

Gnomad AFR AF: 0.00832

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.0396

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0285

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0439

Gnomad OTH AF: 0.0273

GnomAD2 exomes AF: 0.0341 AC: 8558 AN: 251152 AF XY: 0.0330

Gnomad AFR exome AF: 0.00592

Gnomad AMR exome AF: 0.0459

Gnomad ASJ exome AF: 0.0219

Gnomad EAS exome AF: 0.0358

Gnomad FIN exome AF: 0.0322

Gnomad NFE exome AF: 0.0418

Gnomad OTH exome AF: 0.0326

GnomAD4 exome AF: 0.0388 AC: 55692 AN: 1434578 Hom.: 1231 Cov.: 25 AF XY: 0.0380 AC XY: 27198 AN XY: 715154

African (AFR) AF: 0.00635 AC: 209 AN: 32914

American (AMR) AF: 0.0468 AC: 2091 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 561 AN: 25976

East Asian (EAS) AF: 0.0454 AC: 1794 AN: 39542

South Asian (SAS) AF: 0.0121 AC: 1038 AN: 85720

European-Finnish (FIN) AF: 0.0319 AC: 1700 AN: 53244

Middle Eastern (MID) AF: 0.00438 AC: 25 AN: 5712

European-Non Finnish (NFE) AF: 0.0426 AC: 46277 AN: 1087338

Other (OTH) AF: 0.0336 AC: 1997 AN: 59448

GnomAD4 genome AF: 0.0307 AC: 4677 AN: 152324 Hom.: 87 Cov.: 32 AF XY: 0.0311 AC XY: 2313 AN XY: 74492

African (AFR) AF: 0.00830 AC: 345 AN: 41578

American (AMR) AF: 0.0431 AC: 659 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3468

East Asian (EAS) AF: 0.0395 AC: 205 AN: 5190

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4828

European-Finnish (FIN) AF: 0.0285 AC: 303 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0439 AC: 2986 AN: 68034

Other (OTH) AF: 0.0270 AC: 57 AN: 2112

Alfa AF: 0.0360 Hom.: 166

Bravo AF: 0.0310

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia 13 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.40
PhyloP100		-2.9
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: rs2288024; hg19: chr16-84211465; COSMIC: COSV58985333; COSMIC: COSV58985333;