chr6-158999513-G-C

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.38C>G(p.Pro13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00831 in 1,566,622 control chromosomes in the GnomAD database, including 946 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 476 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 470 hom. )

Consequence

RSPH3
NM_031924.8 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.35

Publications

3 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=0.0015439689).

BP6

Variant 6-158999513-G-C is Benign according to our data. Variant chr6-158999513-G-C is described in ClinVar as Benign. ClinVar VariationId is 475833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031924.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RSPH3	NM_031924.8	MANE Select	c.38C>G	p.Pro13Arg	missense	Exon 1 of 8	NP_114130.4
RSPH3	NM_001346418.1		c.464C>G	p.Pro155Arg	missense	Exon 1 of 6	NP_001333347.1
RSPH3	NR_144434.1		n.675C>G		non_coding_transcript_exon	Exon 1 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RSPH3	ENST00000367069.7	TSL:1 MANE Select	c.38C>G	p.Pro13Arg	missense	Exon 1 of 8	ENSP00000356036.1
RSPH3	ENST00000449822.6	TSL:2	c.38C>G	p.Pro13Arg	missense	Exon 1 of 6	ENSP00000393195.1
TAGAP-AS1	ENST00000819074.1		n.279G>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.0440

AC:

6687

AN:

152054

Hom.:

475

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0154

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.0398

GnomAD2 exomes

AF:

0.0128

AC:

2835

AN:

222098

AF XY:

0.00938

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.00742

Gnomad ASJ exome

AF:

0.000279

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000406

Gnomad OTH exome

AF:

0.00534

GnomAD4 exome

AF:

0.00447

AC:

6329

AN:

1414450

Hom.:

470

Cov.:

AF XY:

0.00386

AC XY:

2689

AN XY:

696982

show subpopulations

African (AFR)

AF:

0.158

AC:

5109

AN:

32310

American (AMR)

AF:

0.00889

AC:

362

AN:

40712

Ashkenazi Jewish (ASJ)

AF:

0.000428

AC:

AN:

23360

East Asian (EAS)

AF:

0.00

AC:

AN:

39030

South Asian (SAS)

AF:

0.000285

AC:

AN:

80686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50796

Middle Eastern (MID)

AF:

0.0111

AC:

AN:

5414

European-Non Finnish (NFE)

AF:

0.000192

AC:

208

AN:

1083886

Other (OTH)

AF:

0.00956

AC:

557

AN:

58256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

276

553

829

1106

1382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

162

324

486

648

810

<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:

0.0440

AC:

6694

AN:

152172

Hom.:

476

Cov.:

AF XY:

0.0430

AC XY:

3201

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.153

AC:

6335

AN:

41466

American (AMR)

AF:

0.0154

AC:

235

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

68016

Other (OTH)

AF:

0.0389

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

289

578

867

1156

1445

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:

0.00279

Hom.:

Bravo

AF:

0.0507

ESP6500AA

AF:

0.155

AC:

685

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.0144

AC:

1748

Asia WGS

AF:

0.00924

AC:

AN:

3478

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

Sep 07, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.026

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

PhyloP100

1.4

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.5

REVEL

Benign

0.059

Sift

Benign

0.11

Sift4G

Benign

0.52

Polyphen

0.34

Vest4

0.063

MPC

0.37

ClinPred

0.016

GERP RS

-0.22

PromoterAI

0.073

Neutral

(source)

Varity_R

0.031

gMVP

0.041

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over