16-84178129-A-C

Variant names:

• chr16-84178129-A-C
• rs2288025
• NM_001243156.2:c.*812T>G

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.*812T>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 0.11 in 410,688 control chromosomes in the GnomAD database, including 2,880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (797 hom., cov: 32)
  • Exomes 𝑓: 0.12 (2083 hom.)
• Consequence: TAF1C NM_001243156.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.219
• Publications: 9 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=-0.83).
• BP6: Variant 16-84178129-A-C is Benign according to our data. Variant chr16-84178129-A-C is described in ClinVar as [Benign]. Clinvar id is 1273114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1C	NM_001243156.2	c.*812T>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000566732.6	NP_001230085.2
DNAAF1	NM_178452.6	c.*288A>C		downstream_gene_variant		ENST00000378553.10	NP_848547.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1C	ENST00000566732.6	c.*812T>G		3_prime_UTR_variant	Exon 15 of 15	2	NM_001243156.2	ENSP00000455933.1
DNAAF1	ENST00000378553.10	c.*288A>C		downstream_gene_variant		1	NM_178452.6	ENSP00000367815.5

Frequencies

GnomAD3 genomes AF: 0.0994 AC: 15117 AN: 152044 Hom.: 792 Cov.: 32

Gnomad AFR AF: 0.0912

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.0810

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.115 AC: 29843 AN: 258526 Hom.: 2083 Cov.: 0 AF XY: 0.125 AC XY: 17706 AN XY: 141622

African (AFR) AF: 0.0860 AC: 618 AN: 7186

American (AMR) AF: 0.0689 AC: 973 AN: 14120

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 967 AN: 6776

East Asian (EAS) AF: 0.173 AC: 2109 AN: 12180

South Asian (SAS) AF: 0.205 AC: 8984 AN: 43854

European-Finnish (FIN) AF: 0.0909 AC: 1057 AN: 11628

Middle Eastern (MID) AF: 0.119 AC: 185 AN: 1556

European-Non Finnish (NFE) AF: 0.0913 AC: 13507 AN: 147898

Other (OTH) AF: 0.108 AC: 1443 AN: 13328

GnomAD4 genome AF: 0.0995 AC: 15136 AN: 152162 Hom.: 797 Cov.: 32 AF XY: 0.101 AC XY: 7514 AN XY: 74388

African (AFR) AF: 0.0911 AC: 3782 AN: 41496

American (AMR) AF: 0.0905 AC: 1383 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3466

East Asian (EAS) AF: 0.183 AC: 943 AN: 5154

South Asian (SAS) AF: 0.207 AC: 999 AN: 4824

European-Finnish (FIN) AF: 0.0810 AC: 858 AN: 10590

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0922 AC: 6270 AN: 68024

Other (OTH) AF: 0.123 AC: 259 AN: 2112

Alfa AF: 0.0926 Hom.: 282

Bravo AF: 0.0965

Asia WGS AF: 0.212 AC: 738 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.83
DANN	Benign	0.48
PhyloP100		-0.22
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: rs2288025; hg19: chr16-84211735;