rs149478284

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_080860.4(RSPH1):c.579A>G(p.Arg193Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,613,592 control chromosomes in the GnomAD database, including 1,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 92 hom., cov: 34)

Exomes 𝑓: 0.037 ( 1159 hom. )

Consequence

RSPH1
NM_080860.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.08

Publications

5 publications found

Variant links:

Genes affected

RSPH1 (HGNC:12371): (radial spoke head component 1) This gene encodes a male meiotic metaphase chromosome-associated acidic protein. This gene is expressed in tissues with motile cilia or flagella, including the trachea, lungs, airway brushings, and testes. Mutations in this gene result in primary ciliary dyskinesia-24. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

RSPH1 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 24
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RSPH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 21-42477439-T-C is Benign according to our data. Variant chr21-42477439-T-C is described in ClinVar as Benign. ClinVar VariationId is 227051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.09 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0296 (4515/152390) while in subpopulation NFE AF = 0.0415 (2822/68030). AF 95% confidence interval is 0.0402. There are 92 homozygotes in GnomAd4. There are 2265 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 92 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH1	NM_080860.4 link	c.579A>G	p.Arg193Arg	synonymous_variant	Exon 7 of 9	ENST00000291536.8	NP_543136.1	Q8WYR4-1
RSPH1	NM_001286506.2 link	c.465A>G	p.Arg155Arg	synonymous_variant	Exon 6 of 8		NP_001273435.1	Q8WYR4-2
RSPH1	XM_011529786.2 link	c.507A>G	p.Arg169Arg	synonymous_variant	Exon 6 of 8		XP_011528088.1
RSPH1	XM_005261208.3 link	c.372A>G	p.Arg124Arg	synonymous_variant	Exon 5 of 7		XP_005261265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RSPH1	ENST00000291536.8 link	c.579A>G	p.Arg193Arg	synonymous_variant	Exon 7 of 9	1	NM_080860.4	ENSP00000291536.3	Q8WYR4-1
RSPH1	ENST00000398352.3 link	c.465A>G	p.Arg155Arg	synonymous_variant	Exon 6 of 8	5		ENSP00000381395.3	Q8WYR4-2
RSPH1	ENST00000493019.1 link	n.2197A>G		non_coding_transcript_exon_variant	Exon 6 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.0297

AC:

4520

AN:

152272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00694

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0224

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0329

Gnomad FIN

AF:

0.0533

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0415

Gnomad OTH

AF:

0.0339

GnomAD2 exomes

AF:

0.0336

AC:

8435

AN:

251312

AF XY:

0.0356

show subpopulations

Gnomad AFR exome

AF:

0.00622

Gnomad AMR exome

AF:

0.0176

Gnomad ASJ exome

AF:

0.0613

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0501

Gnomad NFE exome

AF:

0.0397

Gnomad OTH exome

AF:

0.0365

GnomAD4 exome

AF:

0.0369

AC:

53934

AN:

1461202

Hom.:

1159

Cov.:

AF XY:

0.0375

AC XY:

27274

AN XY:

726916

show subpopulations

African (AFR)

AF:

0.00535

AC:

179

AN:

33474

American (AMR)

AF:

0.0187

AC:

836

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0615

AC:

1608

AN:

26128

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0411

AC:

3540

AN:

86232

European-Finnish (FIN)

AF:

0.0483

AC:

2579

AN:

53352

Middle Eastern (MID)

AF:

0.0392

AC:

226

AN:

5766

European-Non Finnish (NFE)

AF:

0.0385

AC:

42751

AN:

1111446

Other (OTH)

AF:

0.0366

AC:

2212

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

2431

4863

7294

9726

12157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1532

3064

4596

6128

7660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0296

AC:

4515

AN:

152390

Hom.:

Cov.:

AF XY:

0.0304

AC XY:

2265

AN XY:

74524

show subpopulations

African (AFR)

AF:

0.00690

AC:

287

AN:

41606

American (AMR)

AF:

0.0223

AC:

342

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.0608

AC:

211

AN:

3472

East Asian (EAS)

AF:

0.000578

AC:

AN:

5194

South Asian (SAS)

AF:

0.0327

AC:

158

AN:

4832

European-Finnish (FIN)

AF:

0.0533

AC:

566

AN:

10620

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0415

AC:

2822

AN:

68030

Other (OTH)

AF:

0.0336

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

235

471

706

942

1177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0378

Hom.:

Bravo

AF:

0.0261

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0405

EpiControl

AF:

0.0418

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 06, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Arg193Arg in exon 7 of RSPH1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 4.4% (376/8600) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs149478284). -

Primary ciliary dyskinesia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.0

(source)

DANN

Benign

0.73

PhyloP100

2.1

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over