NM_145045.5:c.729C>T

Variant names:

• chr19-11426557-G-A
• rs11879596
• NM_145045.5:c.729C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_145045.5(ODAD3):​c.729C>T​(p.Asn243Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,614,060 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (17 hom., cov: 31)
  • Exomes 𝑓: 0.014 (160 hom.)
• Consequence: ODAD3 NM_145045.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.162
• Publications: 7 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]

PRKCSH (HGNC:9411): (PRKCSH beta subunit of glucosidase II) This gene encodes the beta-subunit of glucosidase II, an N-linked glycan-processing enzyme in the endoplasmic reticulum. The encoded protein is an acidic phosphoprotein known to be a substrate for protein kinase C. Mutations in this gene have been associated with the autosomal dominant polycystic liver disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

PRKCSH Gene-Disease associations (from GenCC):

• polycystic liver disease 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-11426557-G-A is Benign according to our data. Variant chr19-11426557-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.162 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0115 (1747/152218) while in subpopulation NFE AF = 0.0163 (1107/67996). AF 95% confidence interval is 0.0155. There are 17 homozygotes in GnomAd4. There are 824 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 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.729C>T	p.Asn243Asn	synonymous	Exon 6 of 13	NP_659482.3
	ODAD3	NM_001302453.1		c.567C>T	p.Asn189Asn	synonymous	Exon 6 of 13	NP_001289382.1	A5D8V7-2
	ODAD3	NM_001302454.2		c.549C>T	p.Asn183Asn	synonymous	Exon 4 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.729C>T	p.Asn243Asn	synonymous	Exon 6 of 13	ENSP00000348757.3	A5D8V7-1
	ODAD3	ENST00000591179.5	TSL:1	c.549C>T	p.Asn183Asn	synonymous	Exon 4 of 11	ENSP00000466800.1	K7EN59
	ODAD3	ENST00000861507.1		c.627C>T	p.Asn209Asn	synonymous	Exon 5 of 12	ENSP00000531566.1

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1743 AN: 152100 Hom.: 17 Cov.: 31

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.00852

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0163

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.0123 AC: 3061 AN: 249360 AF XY: 0.0128

Gnomad AFR exome AF: 0.00194

Gnomad AMR exome AF: 0.00606

Gnomad ASJ exome AF: 0.00647

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0237

Gnomad NFE exome AF: 0.0158

Gnomad OTH exome AF: 0.0154

GnomAD4 exome AF: 0.0140 AC: 20503 AN: 1461842 Hom.: 160 Cov.: 33 AF XY: 0.0141 AC XY: 10268 AN XY: 727224

African (AFR) AF: 0.00209 AC: 70 AN: 33480

American (AMR) AF: 0.00644 AC: 288 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00670 AC: 175 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0116 AC: 1001 AN: 86258

European-Finnish (FIN) AF: 0.0234 AC: 1251 AN: 53412

Middle Eastern (MID) AF: 0.0116 AC: 67 AN: 5766

European-Non Finnish (NFE) AF: 0.0151 AC: 16826 AN: 1111984

Other (OTH) AF: 0.0136 AC: 824 AN: 60392

GnomAD4 genome AF: 0.0115 AC: 1747 AN: 152218 Hom.: 17 Cov.: 31 AF XY: 0.0111 AC XY: 824 AN XY: 74420

African (AFR) AF: 0.00229 AC: 95 AN: 41534

American (AMR) AF: 0.00851 AC: 130 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 15 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0101 AC: 49 AN: 4828

European-Finnish (FIN) AF: 0.0242 AC: 257 AN: 10614

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0163 AC: 1107 AN: 67996

Other (OTH) AF: 0.0109 AC: 23 AN: 2104

Alfa AF: 0.0133 Hom.: 46

Bravo AF: 0.0102

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0167

EpiControl AF: 0.0163

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia 30 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.56
PhyloP100		0.16
Mutation Taster		=99/1	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: rs11879596; hg19: chr19-11537377; COSMIC: COSV62699599; COSMIC: COSV62699599;