NM_145045.5:c.*101G>C

Variant names:

• chr19-11420734-C-G
• rs370633080
• NM_145045.5:c.*101G>C

Variant summary

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

The NM_145045.5(ODAD3):​c.*101G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00951 in 1,023,654 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0078 (9 hom., cov: 31)
  • Exomes 𝑓: 0.0098 (52 hom.)
• Consequence: ODAD3 NM_145045.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.26
• Publications: 2 publications found

Genes affected

ODAD3 (HGNC:28303): (outer dynein arm docking complex subunit 3) This gene encodes a protein containing coiled-coil domains. The encoded protein functions in outer dynein arm assembly and is required for motile cilia function. Mutations in this gene result in primary ciliary dyskinesia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

ODAD3 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 30

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• 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=-0.74).
• BP6: Variant 19-11420734-C-G is Benign according to our data. Variant chr19-11420734-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1215607.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00783 (1192/152326) while in subpopulation NFE AF = 0.0119 (810/68026). AF 95% confidence interval is 0.0112. There are 9 homozygotes in GnomAd4. There are 564 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145045.5. 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
	ODAD3	NM_145045.5	MANE Select	c.*101G>C		3_prime_UTR	Exon 13 of 13	NP_659482.3
	ODAD3	NM_001302453.1		c.*101G>C		3_prime_UTR	Exon 13 of 13	NP_001289382.1	A5D8V7-2
	ODAD3	NM_001302454.2		c.*101G>C		3_prime_UTR	Exon 11 of 11	NP_001289383.1	K7EN59

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD3	ENST00000356392.9	TSL:1 MANE Select	c.*101G>C		3_prime_UTR	Exon 13 of 13	ENSP00000348757.3	A5D8V7-1
	ODAD3	ENST00000591179.5	TSL:1	c.*101G>C		3_prime_UTR	Exon 11 of 11	ENSP00000466800.1	K7EN59
	ODAD3	ENST00000861507.1		c.*101G>C		3_prime_UTR	Exon 12 of 12	ENSP00000531566.1

Frequencies

GnomAD3 genomes AF: 0.00784 AC: 1193 AN: 152208 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.00268

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0119

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.00980 AC: 8543 AN: 871328 Hom.: 52 Cov.: 12 AF XY: 0.00948 AC XY: 4260 AN XY: 449224

African (AFR) AF: 0.00210 AC: 45 AN: 21460

American (AMR) AF: 0.00197 AC: 62 AN: 31490

Ashkenazi Jewish (ASJ) AF: 0.000873 AC: 17 AN: 19468

East Asian (EAS) AF: 0.00 AC: 0 AN: 36098

South Asian (SAS) AF: 0.00157 AC: 108 AN: 68954

European-Finnish (FIN) AF: 0.0157 AC: 667 AN: 42522

Middle Eastern (MID) AF: 0.00119 AC: 4 AN: 3374

European-Non Finnish (NFE) AF: 0.0121 AC: 7345 AN: 607590

Other (OTH) AF: 0.00731 AC: 295 AN: 40372

GnomAD4 genome AF: 0.00783 AC: 1192 AN: 152326 Hom.: 9 Cov.: 31 AF XY: 0.00757 AC XY: 564 AN XY: 74488

African (AFR) AF: 0.00267 AC: 111 AN: 41586

American (AMR) AF: 0.00333 AC: 51 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4822

European-Finnish (FIN) AF: 0.0161 AC: 171 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0119 AC: 810 AN: 68026

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00294 Hom.: 0

Bravo AF: 0.00657

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.75
DANN	Benign	0.35
PhyloP100		-2.3
Mutation Taster		=100/0	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: rs370633080; hg19: chr19-11531402;