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

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: 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 [Likely_benign]. Clinvar id is 262932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-84177859-T-C is described in Lovd as [Benign].
• 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1C	NM_001243156.2	c.*1082A>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000566732.6	NP_001230085.2
DNAAF1	NM_178452.6	c.*18T>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000378553.10	NP_848547.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1C	ENST00000566732.6	c.*1082A>G		3_prime_UTR_variant	Exon 15 of 15	2	NM_001243156.2	ENSP00000455933.1
DNAAF1	ENST00000378553.10	c.*18T>C		3_prime_UTR_variant	Exon 12 of 12	1	NM_178452.6	ENSP00000367815.5

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

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 24, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31213628) -

Nov 22, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 13 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

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

Publications

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Other links and lift over

dbSNP: rs2288024; hg19: chr16-84211465; COSMIC: COSV58985333; COSMIC: COSV58985333;