rs41267753

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031924.8(RSPH3):c.211C>T(p.Arg71Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0288 in 1,609,950 control chromosomes in the GnomAD database, including 1,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R71Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.053 ( 380 hom., cov: 32)

Exomes 𝑓: 0.026 ( 801 hom. )

Consequence

RSPH3
NM_031924.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.13

Publications

10 publications found

Variant links:

Genes affected

RSPH3 (HGNC:21054): (radial spoke head 3) The protein encoded by this gene acts as a protein kinase A anchoring protein. Mutations in this gene cause primary ciliary dyskinesia; a disorder characterized by defects of the axoneme in motile cilia and sperm flagella. The homolog of this gene was first identified in the blue-green algae Chlamydomonas as encoding a radial spoke protein that formed a structural component of motile cilia and flagella. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2016]

RSPH3 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 32
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Ambry Genetics
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RSPH3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.002583176).

BP6

Variant 6-158986415-G-A is Benign according to our data. Variant chr6-158986415-G-A is described in ClinVar as Benign. ClinVar VariationId is 475835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH3	NM_031924.8 link	c.211C>T	p.Arg71Trp	missense_variant	Exon 3 of 8	ENST00000367069.7	NP_114130.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPH3	ENST00000367069.7 link	c.211C>T	p.Arg71Trp	missense_variant	Exon 3 of 8	1	NM_031924.8	ENSP00000356036.1
RSPH3	ENST00000449822.6 link	c.205-3727C>T		intron_variant	Intron 2 of 5	2		ENSP00000393195.1

Frequencies

GnomAD3 genomes

AF:

0.0533

AC:

8113

AN:

152094

Hom.:

379

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0265

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0226

Gnomad FIN

AF:

0.0335

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0247

Gnomad OTH

AF:

0.0502

GnomAD2 exomes

AF:

0.0293

AC:

7280

AN:

248750

AF XY:

0.0278

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.0146

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.000384

Gnomad FIN exome

AF:

0.0365

Gnomad NFE exome

AF:

0.0258

Gnomad OTH exome

AF:

0.0294

GnomAD4 exome

AF:

0.0262

AC:

38206

AN:

1457738

Hom.:

801

Cov.:

AF XY:

0.0259

AC XY:

18788

AN XY:

725442

show subpopulations

African (AFR)

AF:

0.130

AC:

4300

AN:

33172

American (AMR)

AF:

0.0162

AC:

713

AN:

43982

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

330

AN:

25988

East Asian (EAS)

AF:

0.000277

AC:

AN:

39652

South Asian (SAS)

AF:

0.0227

AC:

1950

AN:

85838

European-Finnish (FIN)

AF:

0.0363

AC:

1937

AN:

53382

Middle Eastern (MID)

AF:

0.0381

AC:

219

AN:

5754

European-Non Finnish (NFE)

AF:

0.0241

AC:

26734

AN:

1109754

Other (OTH)

AF:

0.0334

AC:

2012

AN:

60216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

1590

3181

4771

6362

7952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1048

2096

3144

4192

5240

<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:

0.0534

AC:

8132

AN:

152212

Hom.:

380

Cov.:

AF XY:

0.0512

AC XY:

3807

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.130

AC:

5414

AN:

41504

American (AMR)

AF:

0.0264

AC:

404

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.0224

AC:

108

AN:

4820

European-Finnish (FIN)

AF:

0.0335

AC:

355

AN:

10604

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0247

AC:

1677

AN:

68014

Other (OTH)

AF:

0.0497

AC:

105

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

379

759

1138

1518

1897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0324

Hom.:

358

Bravo

AF:

0.0561

TwinsUK

AF:

0.0235

AC:

ALSPAC

AF:

0.0259

AC:

100

ESP6500AA

AF:

0.124

AC:

548

ESP6500EA

AF:

0.0245

AC:

211

ExAC

AF:

0.0325

AC:

3951

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0246

EpiControl

AF:

0.0240

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 32

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Dec 17, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.57

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

T;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.1

.;L

PhyloP100

4.1

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.99

.;D

Vest4

0.13

MPC

0.82

ClinPred

0.015

GERP RS

5.6

Varity_R

0.14

gMVP

0.13

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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