chr16-84177877-C-T

Position:

chr16-84177877-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.13

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TAF1C	NM_001243156.2 linkuse as main transcript	c.*1064G>A		3_prime_UTR_variant	15/15	ENST00000566732.6
DNAAF1	NM_178452.6 linkuse as main transcript	c.*36C>T		3_prime_UTR_variant	12/12	ENST00000378553.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF1	ENST00000378553.10 linkuse as main transcript	c.*36C>T		3_prime_UTR_variant	12/12	1	NM_178452.6	P1	Q8NEP3-1
TAF1C	ENST00000566732.6 linkuse as main transcript	c.*1064G>A		3_prime_UTR_variant	15/15	2	NM_001243156.2	P2	Q15572-6

Frequencies

GnomAD3 genomes

AF:

0.496

AC:

75298

AN:

151898

Hom.:

18567

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.512

AC:

127937

AN:

250006

Hom.:

32953

AF XY:

0.511

AC XY:

69190

AN XY:

135270

show subpopulations

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 SAS exome

AF:

0.525

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.:

AF XY:

0.502

AC XY:

347770

AN XY:

693240

show subpopulations

Gnomad4 AFR exome

AF:

0.475

Gnomad4 AMR exome

AF:

0.573

Gnomad4 ASJ exome

AF:

0.522

Gnomad4 EAS exome

AF:

0.523

Gnomad4 SAS exome

AF:

0.523

Gnomad4 FIN exome

AF:

0.472

Gnomad4 NFE exome

AF:

0.498

Gnomad4 OTH exome

AF:

0.503

GnomAD4 genome

AF:

0.496

AC:

75384

AN:

152016

Hom.:

18606

Cov.:

AF XY:

0.497

AC XY:

36905

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.480

Gnomad4 AMR

AF:

0.542

Gnomad4 ASJ

AF:

0.524

Gnomad4 EAS

AF:

0.524

Gnomad4 SAS

AF:

0.522

Gnomad4 FIN

AF:

0.466

Gnomad4 NFE

AF:

0.493

Gnomad4 OTH

AF:

0.504

Alfa

AF:

0.497

Hom.:

9470

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

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 13

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.58

DANN

Benign

0.54

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