rs2288024

Positions:

chr16-84177859-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.92

Variant links:

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]

TAF1C links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 87 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF1C	NM_001243156.2 linkuse as main transcript	c.*1082A>G		3_prime_UTR_variant	15/15	ENST00000566732.6	NP_001230085.2
DNAAF1	NM_178452.6 linkuse as main transcript	c.*18T>C		3_prime_UTR_variant	12/12	ENST00000378553.10	NP_848547.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10 linkuse as main transcript	c.*18T>C		3_prime_UTR_variant	12/12	1	NM_178452.6	ENSP00000367815	P1	Q8NEP3-1
TAF1C	ENST00000566732.6 linkuse as main transcript	c.*1082A>G		3_prime_UTR_variant	15/15	2	NM_001243156.2	ENSP00000455933	P2	Q15572-6

Frequencies

GnomAD3 genomes

AF:

0.0308

AC:

4681

AN:

152206

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0341

AC:

8558

AN:

251152

Hom.:

192

AF XY:

0.0330

AC XY:

4475

AN XY:

135794

show subpopulations

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 SAS exome

AF:

0.0117

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.:

AF XY:

0.0380

AC XY:

27198

AN XY:

715154

show subpopulations

Gnomad4 AFR exome

AF:

0.00635

Gnomad4 AMR exome

AF:

0.0468

Gnomad4 ASJ exome

AF:

0.0216

Gnomad4 EAS exome

AF:

0.0454

Gnomad4 SAS exome

AF:

0.0121

Gnomad4 FIN exome

AF:

0.0319

Gnomad4 NFE exome

AF:

0.0426

Gnomad4 OTH exome

AF:

0.0336

GnomAD4 genome

AF:

0.0307

AC:

4677

AN:

152324

Hom.:

Cov.:

AF XY:

0.0311

AC XY:

2313

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00830

Gnomad4 AMR

AF:

0.0431

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.0395

Gnomad4 SAS

AF:

0.0112

Gnomad4 FIN

AF:

0.0285

Gnomad4 NFE

AF:

0.0439

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0371

Hom.:

119

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

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 24, 2019	This variant is associated with the following publications: (PMID: 31213628) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Primary ciliary dyskinesia 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over