rs61739927

Variant names:

• chr19-11430719-G-C
• rs61739927
• NM_145045.5:c.424C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-11430719-G-C
• chr19-11430719-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_145045.5(ODAD3):​c.424C>G​(p.Leu142Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0085 in 1,614,046 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (64 hom.)
• Consequence: ODAD3 NM_145045.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.07
• Publications: 9 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010106593).
• BP6: Variant 19-11430719-G-C is Benign according to our data. Variant chr19-11430719-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 414138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0119 (1816/152174) while in subpopulation AFR AF = 0.0233 (966/41522). AF 95% confidence interval is 0.022. There are 26 homozygotes in GnomAd4. There are 921 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD3	NM_145045.5	MANE Select	c.424C>G	p.Leu142Val	missense	Exon 3 of 13	NP_659482.3
	ODAD3	NM_001302453.1		c.262C>G	p.Leu88Val	missense	Exon 3 of 13	NP_001289382.1
	ODAD3	NM_001302454.2		c.366+180C>G		intron	N/A	NP_001289383.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD3	ENST00000356392.9	TSL:1 MANE Select	c.424C>G	p.Leu142Val	missense	Exon 3 of 13	ENSP00000348757.3
	ODAD3	ENST00000591179.5	TSL:1	c.366+180C>G		intron	N/A	ENSP00000466800.1
	ODAD3	ENST00000861507.1		c.424C>G	p.Leu142Val	missense	Exon 3 of 12	ENSP00000531566.1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1787 AN: 152056 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0228

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.00525

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00792

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.00735

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00772

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00794 AC: 1981 AN: 249508 AF XY: 0.00825

Gnomad AFR exome AF: 0.0246

Gnomad AMR exome AF: 0.00237

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00795

Gnomad FIN exome AF: 0.00672

Gnomad NFE exome AF: 0.00719

Gnomad OTH exome AF: 0.00727

GnomAD4 exome AF: 0.00814 AC: 11900 AN: 1461872 Hom.: 64 Cov.: 31 AF XY: 0.00830 AC XY: 6038 AN XY: 727234

African (AFR) AF: 0.0252 AC: 844 AN: 33480

American (AMR) AF: 0.00284 AC: 127 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00411 AC: 163 AN: 39700

South Asian (SAS) AF: 0.0129 AC: 1117 AN: 86258

European-Finnish (FIN) AF: 0.00545 AC: 291 AN: 53420

Middle Eastern (MID) AF: 0.00745 AC: 43 AN: 5768

European-Non Finnish (NFE) AF: 0.00795 AC: 8844 AN: 1111994

Other (OTH) AF: 0.00778 AC: 470 AN: 60392

GnomAD4 genome AF: 0.0119 AC: 1816 AN: 152174 Hom.: 26 Cov.: 32 AF XY: 0.0124 AC XY: 921 AN XY: 74386

African (AFR) AF: 0.0233 AC: 966 AN: 41522

American (AMR) AF: 0.00524 AC: 80 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00794 AC: 41 AN: 5166

South Asian (SAS) AF: 0.0131 AC: 63 AN: 4818

European-Finnish (FIN) AF: 0.00735 AC: 78 AN: 10608

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

European-Non Finnish (NFE) AF: 0.00772 AC: 525 AN: 68018

Other (OTH) AF: 0.00948 AC: 20 AN: 2110

Alfa AF: 0.00812 Hom.: 1

Bravo AF: 0.0124

TwinsUK AF: 0.0116 AC: 43

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.0219 AC: 91

ESP6500EA AF: 0.00704 AC: 59

ExAC AF: 0.00839 AC: 1015

Asia WGS AF: 0.0150 AC: 53 AN: 3478

EpiCase AF: 0.00545

EpiControl AF: 0.00741

ClinVar

ClinVar submissions as Germline

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
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.1
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.34
Sift	Benign	0.11	T
Sift4G	Benign	0.29	T
Polyphen		0.95	P
Vest4		0.49
MVP		0.81
MPC		1.2
ClinPred		0.013	T
GERP RS		0.47
Varity_R		0.069
gMVP		0.18
Mutation Taster		=298/2	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: rs61739927; hg19: chr19-11541539; COSMIC: COSV52953573; COSMIC: COSV52953573;