dbSNP rs34725942: RSPH3:p.Arg81Arg (chr6-158986383-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_031924.8(RSPH3):c.243G>A(p.Arg81Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,613,380 control chromosomes in the GnomAD database, including 907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 251 hom., cov: 32)

Exomes 𝑓: 0.026 ( 656 hom. )

Consequence

RSPH3
NM_031924.8 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.368

Publications

2 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: ClinGen, PanelApp Australia, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 6-158986383-C-T is Benign according to our data. Variant chr6-158986383-C-T is described in ClinVar as Benign. ClinVar VariationId is 475837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.368 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0992 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	UniProt
RSPH3	NM_031924.8	MANE Select	c.243G>A	p.Arg81Arg	synonymous	Exon 3 of 8	NP_114130.4
RSPH3	NM_001346418.1		c.631-3695G>A		intron	N/A	NP_001333347.1	Q86UC2-2
RSPH3	NR_144434.1		n.880G>A		non_coding_transcript_exon	Exon 3 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RSPH3	ENST00000367069.7	TSL:1 MANE Select	c.243G>A	p.Arg81Arg	synonymous	Exon 3 of 8	ENSP00000356036.1	A0A0C4DFU3
RSPH3	ENST00000884885.1		c.243G>A	p.Arg81Arg	synonymous	Exon 3 of 7	ENSP00000554944.1
RSPH3	ENST00000449822.6	TSL:2	c.205-3695G>A		intron	N/A	ENSP00000393195.1	A0A0C4DG29

Frequencies

GnomAD3 genomes

AF:

0.0451

AC:

6855

AN:

152156

Hom.:

250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0239

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0222

Gnomad FIN

AF:

0.0333

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0244

Gnomad OTH

AF:

0.0450

GnomAD2 exomes

AF:

0.0270

AC:

6793

AN:

251358

AF XY:

0.0262

show subpopulations

Gnomad AFR exome

AF:

0.0993

Gnomad AMR exome

AF:

0.0132

Gnomad ASJ exome

AF:

0.0130

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.0365

Gnomad NFE exome

AF:

0.0257

Gnomad OTH exome

AF:

0.0289

GnomAD4 exome

AF:

0.0255

AC:

37262

AN:

1461106

Hom.:

656

Cov.:

AF XY:

0.0252

AC XY:

18352

AN XY:

726884

show subpopulations

African (AFR)

AF:

0.100

AC:

3358

AN:

33432

American (AMR)

AF:

0.0146

AC:

651

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0128

AC:

334

AN:

26132

East Asian (EAS)

AF:

0.000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.0224

AC:

1936

AN:

86242

European-Finnish (FIN)

AF:

0.0362

AC:

1936

AN:

53418

Middle Eastern (MID)

AF:

0.0340

AC:

196

AN:

5768

European-Non Finnish (NFE)

AF:

0.0242

AC:

26942

AN:

1111338

Other (OTH)

AF:

0.0315

AC:

1899

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

1705

3410

5115

6820

8525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1044

2088

3132

4176

5220

<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:

0.0451

AC:

6873

AN:

152274

Hom.:

251

Cov.:

AF XY:

0.0432

AC XY:

3217

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.102

AC:

4227

AN:

41544

American (AMR)

AF:

0.0238

AC:

364

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3472

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.0220

AC:

106

AN:

4824

European-Finnish (FIN)

AF:

0.0333

AC:

353

AN:

10610

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0244

AC:

1661

AN:

68014

Other (OTH)

AF:

0.0445

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

336

671

1007

1342

1678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0291

Hom.:

Bravo

AF:

0.0469

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0245

EpiControl

AF:

0.0237

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Primary ciliary dyskinesia 32 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.8

(source)

DANN

Benign

0.52

PhyloP100

0.37

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over