16-84177745-C-A

Variant names:

• chr16-84177745-C-A
• NM_178452.6:c.2082C>A
• DNAAF1 p.Ala694Ala

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_178452.6(DNAAF1):​c.2082C>A​(p.Ala694Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A694A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAAF1 NM_178452.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.31
• Publications: 0 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-4.31 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178452.6. 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
	DNAAF1	NM_178452.6	MANE Select	c.2082C>A	p.Ala694Ala	synonymous	Exon 12 of 12	NP_848547.4
	DNAAF1	NM_001318756.1		c.1374C>A	p.Ala458Ala	synonymous	Exon 8 of 8	NP_001305685.1	Q8NEP3-2
	TAF1C	NM_001243156.2	MANE Select	c.*1196G>T		downstream_gene	N/A	NP_001230085.2	Q15572-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF1	ENST00000378553.10	TSL:1 MANE Select	c.2082C>A	p.Ala694Ala	synonymous	Exon 12 of 12	ENSP00000367815.5	Q8NEP3-1
	DNAAF1	ENST00000963697.1		c.2184C>A	p.Ala728Ala	synonymous	Exon 13 of 13	ENSP00000633756.1
	DNAAF1	ENST00000963694.1		c.2178C>A	p.Ala726Ala	synonymous	Exon 13 of 13	ENSP00000633753.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.15
DANN	Benign	0.62
PhyloP100		-4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-84211351;