NM_012144.4:c.-178G>C

Variant names:

• chr9-34458828-G-C
• rs3802429
• NM_012144.4:c.-178G>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_012144.4(DNAI1):​c.-178G>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 0.0188 in 678,742 control chromosomes in the GnomAD database, including 515 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (93 hom., cov: 32)
  • Exomes 𝑓: 0.018 (422 hom.)
• Consequence: DNAI1 NM_012144.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.15
• Publications: 1 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 9-34458828-G-C is Benign according to our data. Variant chr9-34458828-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 366679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

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.-178G>C		5_prime_UTR	Exon 1 of 20	NP_036276.1	A0A140VJI0
	DNAI1	NM_001281428.2		c.-178G>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.-178G>C		5_prime_UTR	Exon 1 of 20	ENSP00000242317.4	Q9UI46-1
	DNAI1	ENST00000878474.1		c.-178G>C		5_prime_UTR	Exon 1 of 21	ENSP00000548533.1
	DNAI1	ENST00000614641.4	TSL:5	c.-178G>C		5_prime_UTR	Exon 1 of 20	ENSP00000480538.1	A0A087WWV9

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3157 AN: 152220 Hom.: 92 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0267

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.0182 AC: 9558 AN: 526404 Hom.: 422 Cov.: 5 AF XY: 0.0172 AC XY: 4834 AN XY: 281806

African (AFR) AF: 0.0355 AC: 532 AN: 14984

American (AMR) AF: 0.0911 AC: 2936 AN: 32238

Ashkenazi Jewish (ASJ) AF: 0.000169 AC: 3 AN: 17704

East Asian (EAS) AF: 0.110 AC: 3468 AN: 31476

South Asian (SAS) AF: 0.0225 AC: 1305 AN: 58082

European-Finnish (FIN) AF: 0.0120 AC: 462 AN: 38648

Middle Eastern (MID) AF: 0.0105 AC: 30 AN: 2868

European-Non Finnish (NFE) AF: 0.00125 AC: 377 AN: 301406

Other (OTH) AF: 0.0153 AC: 445 AN: 28998

GnomAD4 genome AF: 0.0208 AC: 3175 AN: 152338 Hom.: 93 Cov.: 32 AF XY: 0.0218 AC XY: 1625 AN XY: 74504

African (AFR) AF: 0.0361 AC: 1500 AN: 41576

American (AMR) AF: 0.0424 AC: 649 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.121 AC: 626 AN: 5170

South Asian (SAS) AF: 0.0265 AC: 128 AN: 4832

European-Finnish (FIN) AF: 0.0124 AC: 132 AN: 10630

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00129 AC: 88 AN: 68032

Other (OTH) AF: 0.0203 AC: 43 AN: 2116

Alfa AF: 0.0109 Hom.: 6

Bravo AF: 0.0271

Asia WGS AF: 0.0760 AC: 263 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.75
PhyloP100		2.2
PromoterAI		-0.058	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3802429; hg19: chr9-34458826; COSMIC: COSV52622969; COSMIC: COSV52622969;