rs1555721612

Positions:

• chr19-11422703-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000356392.9(ODAD3):​c.1275G>A​(p.Val425=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,460,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: ODAD3 ENST00000356392.9 splice_region, synonymous
• Scores: Splicing: ADA: 0.0002567
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.618

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 19-11422703-C-T is Benign according to our data. Variant chr19-11422703-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 477979.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD3	NM_145045.5	c.1275G>A	p.Val425=	splice_region_variant, synonymous_variant	9/13	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302453.1	c.1113G>A	p.Val371=	splice_region_variant, synonymous_variant	9/13		NP_001289382.1
ODAD3	NM_001302454.2	c.1095G>A	p.Val365=	splice_region_variant, synonymous_variant	7/11		NP_001289383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9	c.1275G>A	p.Val425=	splice_region_variant, synonymous_variant	9/13	1	NM_145045.5	ENSP00000348757	P2
ODAD3	ENST00000591179.5	c.1095G>A	p.Val365=	splice_region_variant, synonymous_variant	7/11	1		ENSP00000466800	A2
ODAD3	ENST00000586836.5	c.702G>A	p.Val234=	splice_region_variant, synonymous_variant	9/13	2		ENSP00000467429	A2
ODAD3	ENST00000591345.5	c.*1194G>A		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	10/14	5		ENSP00000467313

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1460008 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 726338

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 30 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	8.2
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00026
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: 3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555721612; hg19: chr19-11533371; COSMIC: COSV62699614; COSMIC: COSV62699614;