9-34458826-G-C

Variant names:

• chr9-34458826-G-C
• rs180838420
• NM_012144.4:c.-180G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012144.4(DNAI1):​c.-180G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000385 in 519,044 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: 0.0000039 (0 hom.)
• Consequence: DNAI1 NM_012144.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• Publications: 0 publications found

Genes affected

DNAI1 (HGNC:2954): (dynein axonemal intermediate chain 1) This gene encodes a member of the dynein intermediate chain family. The encoded protein is part of the dynein complex in respiratory cilia. The inner- and outer-arm dyneins, which bridge between the doublet microtubules in axonemes, are the force-generating proteins responsible for the sliding movement in axonemes. The intermediate and light chains, thought to form the base of the dynein arm, help mediate attachment and may also participate in regulating dynein activity. Mutations in this gene result in abnormal ciliary ultrastructure and function associated with primary ciliary dyskinesia and Kartagener syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

FAM219A (HGNC:19920): (family with sequence similarity 219 member A) The protein encoded by this gene has homologs that have been identified in mouse, macaque, etc organisms. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012144.4. 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
	DNAI1	NM_012144.4	MANE Select	c.-180G>C		5_prime_UTR	Exon 1 of 20	NP_036276.1	A0A140VJI0
	DNAI1	NM_001281428.2		c.-180G>C		5_prime_UTR	Exon 1 of 20	NP_001268357.1	A0A087WWV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI1	ENST00000242317.9	TSL:1 MANE Select	c.-180G>C		5_prime_UTR	Exon 1 of 20	ENSP00000242317.4	Q9UI46-1
	DNAI1	ENST00000878474.1		c.-180G>C		5_prime_UTR	Exon 1 of 21	ENSP00000548533.1
	DNAI1	ENST00000614641.4	TSL:5	c.-180G>C		5_prime_UTR	Exon 1 of 20	ENSP00000480538.1	A0A087WWV9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000385 AC: 2 AN: 519044 Hom.: 0 Cov.: 5 AF XY: 0.00000722 AC XY: 2 AN XY: 277126

African (AFR) AF: 0.00 AC: 0 AN: 14754

American (AMR) AF: 0.00 AC: 0 AN: 31504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17386

East Asian (EAS) AF: 0.00 AC: 0 AN: 31400

South Asian (SAS) AF: 0.0000349 AC: 2 AN: 57388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2842

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 297118

Other (OTH) AF: 0.00 AC: 0 AN: 28630

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.83
PhyloP100		2.6
PromoterAI		0.098	Neutral

Splicing

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

Other links and lift over

dbSNP: rs180838420; hg19: chr9-34458824;