NM_178452.6:c.-197G>C

Variant names:

• chr16-84145244-G-C
• rs151171498
• NM_178452.6:c.-197G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178452.6(DNAAF1):​c.-197G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 703,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: DNAAF1 NM_178452.6 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• 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]

HSDL1 (HGNC:16475): (hydroxysteroid dehydrogenase like 1) Predicted to enable oxidoreductase activity. Located in intermediate filament cytoskeleton and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6	c.-197G>C		upstream_gene_variant		ENST00000378553.10	NP_848547.4
HSDL1	NM_031463.5	c.-233C>G		upstream_gene_variant		ENST00000219439.9	NP_113651.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10	c.-197G>C		upstream_gene_variant		1	NM_178452.6	ENSP00000367815.5
HSDL1	ENST00000219439.9	c.-233C>G		upstream_gene_variant		1	NM_031463.5	ENSP00000219439.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000284 AC: 2 AN: 703500 Hom.: 0 Cov.: 9 AF XY: 0.00000563 AC XY: 2 AN XY: 355376

African (AFR) AF: 0.00 AC: 0 AN: 15546

American (AMR) AF: 0.00 AC: 0 AN: 20060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14634

East Asian (EAS) AF: 0.00 AC: 0 AN: 28224

South Asian (SAS) AF: 0.00 AC: 0 AN: 50604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2402

European-Non Finnish (NFE) AF: 0.00000391 AC: 2 AN: 511014

Other (OTH) AF: 0.00 AC: 0 AN: 33602

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.8
DANN	Benign	0.33
PhyloP100		1.3
PromoterAI		-0.18	Neutral

Splicing

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

Other links and lift over

dbSNP: rs151171498; hg19: chr16-84178849;