rs1053136709

Variant names:

• chr19-11423958-C-G
• rs1053136709
• NM_145045.5:c.1035G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-11423958-C-G
• chr19-11423958-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS1

The NM_145045.5(ODAD3):​c.1035G>C​(p.Glu345Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: ODAD3 NM_145045.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.507
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26093405).
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.0000103 (15/1461160) while in subpopulation AFR AF = 0.000448 (15/33480). AF 95% confidence interval is 0.000276. There are 0 homozygotes in GnomAdExome4. There are 6 alleles in the male GnomAdExome4 subpopulation. Median coverage is 34. This position passed quality control check.

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.1035G>C	p.Glu345Asp	missense	Exon 8 of 13	NP_659482.3
	ODAD3	NM_001302453.1		c.873G>C	p.Glu291Asp	missense	Exon 8 of 13	NP_001289382.1	A5D8V7-2
	ODAD3	NM_001302454.2		c.855G>C	p.Glu285Asp	missense	Exon 6 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.1035G>C	p.Glu345Asp	missense	Exon 8 of 13	ENSP00000348757.3	A5D8V7-1
	ODAD3	ENST00000591179.5	TSL:1	c.855G>C	p.Glu285Asp	missense	Exon 6 of 11	ENSP00000466800.1	K7EN59
	ODAD3	ENST00000861507.1		c.933G>C	p.Glu311Asp	missense	Exon 7 of 12	ENSP00000531566.1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152072 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000803 AC: 2 AN: 249060 AF XY: 0.00000740

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461160 Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6 AN XY: 726908

African (AFR) AF: 0.000448 AC: 15 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152072 Hom.: 0 Cov.: 30 AF XY: 0.0000539 AC XY: 4 AN XY: 74272

African (AFR) AF: 0.000290 AC: 12 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15248

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000831

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Primary ciliary dyskinesia 30 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.51
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.29
Sift	Benign	0.12	T
Sift4G	Benign	0.20	T
Polyphen		0.95	P
Vest4		0.26
MutPred		0.26		Loss of disorder (P = 0.1865)
MVP		0.72
MPC		0.41
ClinPred		0.20	T
GERP RS		3.1
Varity_R		0.16
gMVP		0.40
Mutation Taster		=97/3	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: rs1053136709; hg19: chr19-11534627;