NM_001243156.2:c.*1064G>A

Variant names:

• chr16-84177877-C-T
• rs8692
• NM_001243156.2:c.*1064G>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.*1064G>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 0.501 in 1,536,582 control chromosomes in the GnomAD database, including 192,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (18606 hom., cov: 32)
  • Exomes 𝑓: 0.50 (174368 hom.)
• Consequence: TAF1C NM_001243156.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.13
• Publications: 24 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: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia
• 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=-0.92).
• BP6: Variant 16-84177877-C-T is Benign according to our data. Variant chr16-84177877-C-T is described in ClinVar as [Benign]. Clinvar id is 262933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1C	NM_001243156.2	c.*1064G>A		3_prime_UTR_variant	Exon 15 of 15	ENST00000566732.6	NP_001230085.2
DNAAF1	NM_178452.6	c.*36C>T		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.*1064G>A		3_prime_UTR_variant	Exon 15 of 15	2	NM_001243156.2	ENSP00000455933.1
DNAAF1	ENST00000378553.10	c.*36C>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_178452.6	ENSP00000367815.5

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75298 AN: 151898 Hom.: 18567 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.502

GnomAD2 exomes AF: 0.512 AC: 127937 AN: 250006 AF XY: 0.511

Gnomad AFR exome AF: 0.476

Gnomad AMR exome AF: 0.574

Gnomad ASJ exome AF: 0.515

Gnomad EAS exome AF: 0.521

Gnomad FIN exome AF: 0.469

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.523

GnomAD4 exome AF: 0.502 AC: 694550 AN: 1384566 Hom.: 174368 Cov.: 21 AF XY: 0.502 AC XY: 347770 AN XY: 693240

African (AFR) AF: 0.475 AC: 15151 AN: 31906

American (AMR) AF: 0.573 AC: 25529 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 13348 AN: 25594

East Asian (EAS) AF: 0.523 AC: 20519 AN: 39264

South Asian (SAS) AF: 0.523 AC: 44378 AN: 84816

European-Finnish (FIN) AF: 0.472 AC: 25038 AN: 53040

Middle Eastern (MID) AF: 0.522 AC: 2924 AN: 5604

European-Non Finnish (NFE) AF: 0.498 AC: 518571 AN: 1041956

Other (OTH) AF: 0.503 AC: 29092 AN: 57812

GnomAD4 genome AF: 0.496 AC: 75384 AN: 152016 Hom.: 18606 Cov.: 32 AF XY: 0.497 AC XY: 36905 AN XY: 74292

African (AFR) AF: 0.480 AC: 19895 AN: 41432

American (AMR) AF: 0.542 AC: 8271 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1819 AN: 3472

East Asian (EAS) AF: 0.524 AC: 2714 AN: 5176

South Asian (SAS) AF: 0.522 AC: 2517 AN: 4820

European-Finnish (FIN) AF: 0.466 AC: 4917 AN: 10546

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33485 AN: 67978

Other (OTH) AF: 0.504 AC: 1065 AN: 2114

Alfa AF: 0.499 Hom.: 10987

Bravo AF: 0.502

Asia WGS AF: 0.527 AC: 1831 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 13 Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 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. -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.58
DANN	Benign	0.54
PhyloP100		-1.1
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: rs8692; hg19: chr16-84211483; COSMIC: COSV58985355; COSMIC: COSV58985355;