rs17426435

Variant names:

• chr19-11435448-G-A
• rs17426435
• ENST00000852992.1:c.-340G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-11435448-G-A
• chr19-11435448-G-C

Variant summary

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

The NM_001302453.1(ODAD3):​c.82+242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 359,886 control chromosomes in the GnomAD database, including 723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (305 hom., cov: 33)
  • Exomes 𝑓: 0.057 (418 hom.)
• Consequence: ODAD3 NM_001302453.1 intron
• Scores: Splicing: ADA: 0.0008653
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.395
• Publications: 8 publications found

Genes affected

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]

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 19-11435448-G-A is Benign according to our data. Variant chr19-11435448-G-A is described in ClinVar as Benign. ClinVar VariationId is 328161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302453.1. 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_001302453.1		c.82+242C>T		intron	N/A	NP_001289382.1	A5D8V7-2
	PRKCSH	NM_001289104.2	MANE Select	c.-336G>A		upstream_gene	N/A	NP_001276033.1	K7ELL7
	PRKCSH	NM_001289103.2		c.-340G>A		upstream_gene	N/A	NP_001276032.1	K7ELL7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCSH	ENST00000852992.1		c.-340G>A		5_prime_UTR	Exon 1 of 18	ENSP00000523051.1
	PRKCSH	ENST00000591946.5	TSL:2	c.-336G>A		5_prime_UTR	Exon 1 of 3	ENSP00000464835.1	K7EIP3
	PRKCSH	ENST00000852989.1		c.-144+5G>A		splice_region intron	N/A	ENSP00000523048.1

Frequencies

GnomAD3 genomes AF: 0.0518 AC: 7879 AN: 152146 Hom.: 305 Cov.: 33

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0581

Gnomad OTH AF: 0.0656

GnomAD4 exome AF: 0.0571 AC: 11853 AN: 207622 Hom.: 418 Cov.: 4 AF XY: 0.0567 AC XY: 6395 AN XY: 112706

African (AFR) AF: 0.0134 AC: 72 AN: 5360

American (AMR) AF: 0.138 AC: 1284 AN: 9322

Ashkenazi Jewish (ASJ) AF: 0.0897 AC: 421 AN: 4694

East Asian (EAS) AF: 0.0293 AC: 212 AN: 7228

South Asian (SAS) AF: 0.0524 AC: 2168 AN: 41396

European-Finnish (FIN) AF: 0.0518 AC: 463 AN: 8932

Middle Eastern (MID) AF: 0.0541 AC: 36 AN: 666

European-Non Finnish (NFE) AF: 0.0552 AC: 6630 AN: 120186

Other (OTH) AF: 0.0576 AC: 567 AN: 9838

GnomAD4 genome AF: 0.0518 AC: 7889 AN: 152264 Hom.: 305 Cov.: 33 AF XY: 0.0521 AC XY: 3881 AN XY: 74432

African (AFR) AF: 0.0140 AC: 583 AN: 41578

American (AMR) AF: 0.121 AC: 1843 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 299 AN: 3468

East Asian (EAS) AF: 0.0237 AC: 123 AN: 5180

South Asian (SAS) AF: 0.0408 AC: 197 AN: 4834

European-Finnish (FIN) AF: 0.0473 AC: 502 AN: 10608

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0582 AC: 3957 AN: 68014

Other (OTH) AF: 0.0649 AC: 137 AN: 2110

Alfa AF: 0.0540 Hom.: 559

Bravo AF: 0.0581

Asia WGS AF: 0.0450 AC: 158 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Polycystic liver disease 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		-0.40
PromoterAI		-0.041	Neutral
Mutation Taster		=85/15	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00087
dbscSNV1_RF	Benign	0.11

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

Other links and lift over

dbSNP: rs17426435; hg19: chr19-11546269;