NM_012144.4:c.-116T>C

Variant names:

• chr9-34458890-T-C
• rs62619982
• NM_012144.4:c.-116T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_012144.4(DNAI1):​c.-116T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 902,200 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00052 (4 hom.)
• Consequence: DNAI1 NM_012144.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.325
• Publications: 2 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]

DNAI1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 1

  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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 9-34458890-T-C is Benign according to our data. Variant chr9-34458890-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 913580.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00391 (595/152328) while in subpopulation AFR AF = 0.0136 (566/41576). AF 95% confidence interval is 0.0127. There are 3 homozygotes in GnomAd4. There are 275 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,AD gene

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.-116T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	NP_036276.1	A0A140VJI0
	DNAI1	NM_012144.4	MANE Select	c.-116T>C		5_prime_UTR	Exon 1 of 20	NP_036276.1	A0A140VJI0
	DNAI1	NM_001281428.2		c.-116T>C		5_prime_UTR_premature_start_codon_gain	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.-116T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	ENSP00000242317.4	Q9UI46-1
	DNAI1	ENST00000242317.9	TSL:1 MANE Select	c.-116T>C		5_prime_UTR	Exon 1 of 20	ENSP00000242317.4	Q9UI46-1
	DNAI1	ENST00000878474.1		c.-116T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	ENSP00000548533.1

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 590 AN: 152210 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.000520 AC: 390 AN: 749872 Hom.: 4 Cov.: 10 AF XY: 0.000419 AC XY: 166 AN XY: 396060

African (AFR) AF: 0.0148 AC: 295 AN: 19872

American (AMR) AF: 0.000830 AC: 31 AN: 37362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21268

East Asian (EAS) AF: 0.00 AC: 0 AN: 35262

South Asian (SAS) AF: 0.000146 AC: 10 AN: 68458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50600

Middle Eastern (MID) AF: 0.000675 AC: 3 AN: 4444

European-Non Finnish (NFE) AF: 0.00000841 AC: 4 AN: 475720

Other (OTH) AF: 0.00127 AC: 47 AN: 36886

GnomAD4 genome AF: 0.00391 AC: 595 AN: 152328 Hom.: 3 Cov.: 32 AF XY: 0.00369 AC XY: 275 AN XY: 74492

African (AFR) AF: 0.0136 AC: 566 AN: 41576

American (AMR) AF: 0.00111 AC: 17 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00272 Hom.: 0

Bravo AF: 0.00423

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Kartagener syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		0.33
PromoterAI		-0.038	Neutral
Mutation Taster		=300/0	polymorphism

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: rs62619982; hg19: chr9-34458888;