rs61750777

Variant names:

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.35C>T(p.Ala12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00414 in 1,571,204 control chromosomes in the GnomAD database, including 210 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 102 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 108 hom. )

Consequence

RSPH3
NM_031924.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.638

Publications

4 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 links:

TAGAP-AS1 (HGNC:55239): (TAGAP antisense RNA 1)

TAGAP-AS1 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=0.0020791888).

BP6

Variant 6-158999516-G-A is Benign according to our data. Variant chr6-158999516-G-A is described in ClinVar as [Benign]. Clinvar id is 475832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH3	NM_031924.8 link	c.35C>T	p.Ala12Val	missense_variant	Exon 1 of 8	ENST00000367069.7	NP_114130.4	Q86UC2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPH3	ENST00000367069.7 link	c.35C>T	p.Ala12Val	missense_variant	Exon 1 of 8	1	NM_031924.8	ENSP00000356036.1		A0A0C4DFU3

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3224

AN:

152080

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0738

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0196

GnomAD2 exomes

AF:

0.00654

AC:

1475

AN:

225590

AF XY:

0.00490

show subpopulations

Gnomad AFR exome

AF:

0.0766

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.000266

Gnomad EAS exome

AF:

0.00414

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000205

Gnomad OTH exome

AF:

0.00298

GnomAD4 exome

AF:

0.00231

AC:

3281

AN:

1419006

Hom.:

108

Cov.:

AF XY:

0.00198

AC XY:

1383

AN XY:

699656

show subpopulations

African (AFR)

AF:

0.0784

AC:

2551

AN:

32532

American (AMR)

AF:

0.00456

AC:

189

AN:

41466

Ashkenazi Jewish (ASJ)

AF:

0.000423

AC:

AN:

23650

East Asian (EAS)

AF:

0.00217

AC:

AN:

39082

South Asian (SAS)

AF:

0.000148

AC:

AN:

81154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51128

Middle Eastern (MID)

AF:

0.00677

AC:

AN:

5468

European-Non Finnish (NFE)

AF:

0.0000930

AC:

101

AN:

1086080

Other (OTH)

AF:

0.00506

AC:

296

AN:

58446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

164

328

493

657

821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0212

AC:

3228

AN:

152198

Hom.:

102

Cov.:

AF XY:

0.0206

AC XY:

1530

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0736

AC:

3056

AN:

41500

American (AMR)

AF:

0.00673

AC:

103

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00290

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68002

Other (OTH)

AF:

0.0194

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

158

316

475

633

791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00874

Hom.:

Bravo

AF:

0.0232

ESP6500AA

AF:

0.0697

AC:

307

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00692

AC:

839

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 32

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Dec 31, 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

0.094

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

T;.;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.66

T;T;T

MetaRNN

Benign

0.0021

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;.;L

PhyloP100

0.64

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.055

Sift

Uncertain

0.026

D;D;D

Sift4G

Benign

0.075

T;T;D

Polyphen

0.055

.;.;B

Vest4

0.058

MVP

0.13

MPC

0.31

ClinPred

0.036

GERP RS

4.4

PromoterAI

-0.073

Neutral

(source)

Varity_R

0.12

gMVP

0.086

Mutation Taster

=86/14

polymorphism (auto)

(source)

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

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