rs8692

Variant names:

• chr16-84177877-C-T
• rs8692
• NM_001243156.2:c.*1064G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-84177877-C-T
• chr16-84177877-C-A
• chr16-84177877-C-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.*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: ClinGen, Labcorp Genetics (formerly Invitae)
• 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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243156.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1C	NM_001243156.2	MANE Select	c.*1064G>A		3_prime_UTR	Exon 15 of 15	NP_001230085.2	Q15572-6
	DNAAF1	NM_178452.6	MANE Select	c.*36C>T		3_prime_UTR	Exon 12 of 12	NP_848547.4
	TAF1C	NM_005679.4		c.*1064G>A		3_prime_UTR	Exon 14 of 14	NP_005670.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1C	ENST00000566732.6	TSL:2 MANE Select	c.*1064G>A		3_prime_UTR	Exon 15 of 15	ENSP00000455933.1	Q15572-6
	DNAAF1	ENST00000378553.10	TSL:1 MANE Select	c.*36C>T		3_prime_UTR	Exon 12 of 12	ENSP00000367815.5	Q8NEP3-1
	TAF1C	ENST00000341690.10	TSL:1	c.*1064G>A		3_prime_UTR	Exon 15 of 15	ENSP00000345305.6	Q15572-2

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia 13 (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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;