rs13213314

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_001010892.3(RSPH4A):c.446C>G(p.Thr149Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,614,118 control chromosomes in the GnomAD database, including 10,134 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 0.078 ( 662 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9472 hom. )

Consequence

RSPH4A
NM_001010892.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.617

Publications

14 publications found

Variant links:

Genes affected

RSPH4A (HGNC:21558): (radial spoke head component 4A) This gene encodes a protein that appears to be a component the radial spoke head, as determined by homology to similar proteins in the biflagellate alga Chlamydomonas reinhardtii and other ciliates. Radial spokes, which are regularly spaced along cilia, sperm, and flagella axonemes, consist of a thin 'stalk' and a bulbous 'head' that form a signal transduction scaffold between the central pair of microtubules and dynein. Mutations in this gene cause primary ciliary dyskinesia 1, a disease arising from dysmotility of motile cilia and sperm. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

RSPH4A Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 11
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RSPH4A 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=0.0016322434).

BP6

Variant 6-116617069-C-G is Benign according to our data. Variant chr6-116617069-C-G is described in ClinVar as Benign. ClinVar VariationId is 178799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010892.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH4A	NM_001010892.3	MANE Select	c.446C>G	p.Thr149Ser	missense	Exon 1 of 6	NP_001010892.1	Q5TD94-1
	RSPH4A	NM_001161664.2		c.446C>G	p.Thr149Ser	missense	Exon 1 of 5	NP_001155136.1	Q5TD94-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RSPH4A	ENST00000229554.10	TSL:1 MANE Select	c.446C>G	p.Thr149Ser	missense	Exon 1 of 6	ENSP00000229554.5	Q5TD94-1
RSPH4A	ENST00000368581.8	TSL:1	c.446C>G	p.Thr149Ser	missense	Exon 1 of 5	ENSP00000357570.4	Q5TD94-3
RSPH4A	ENST00000368580.4	TSL:5	c.446C>G	p.Thr149Ser	missense	Exon 1 of 5	ENSP00000357569.4	Q5TD94-2

Frequencies

GnomAD3 genomes

AF:

0.0784

AC:

11923

AN:

152150

Hom.:

662

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0217

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.0676

Gnomad ASJ

AF:

0.0778

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0234

Gnomad FIN

AF:

0.0776

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.0837

GnomAD2 exomes

AF:

0.0803

AC:

20182

AN:

251352

AF XY:

0.0812

show subpopulations

Gnomad AFR exome

AF:

0.0199

Gnomad AMR exome

AF:

0.0517

Gnomad ASJ exome

AF:

0.0788

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.0846

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.0940

GnomAD4 exome

AF:

0.108

AC:

157392

AN:

1461850

Hom.:

9472

Cov.:

AF XY:

0.106

AC XY:

76816

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.0172

AC:

576

AN:

33478

American (AMR)

AF:

0.0553

AC:

2475

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0761

AC:

1989

AN:

26136

East Asian (EAS)

AF:

0.000403

AC:

AN:

39700

South Asian (SAS)

AF:

0.0325

AC:

2804

AN:

86258

European-Finnish (FIN)

AF:

0.0907

AC:

4843

AN:

53420

Middle Eastern (MID)

AF:

0.0874

AC:

504

AN:

5768

European-Non Finnish (NFE)

AF:

0.124

AC:

138348

AN:

1111970

Other (OTH)

AF:

0.0966

AC:

5837

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

8753

17507

26260

35014

43767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4782

9564

14346

19128

23910

<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:

0.0783

AC:

11921

AN:

152268

Hom.:

662

Cov.:

AF XY:

0.0743

AC XY:

5533

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0217

AC:

902

AN:

41560

American (AMR)

AF:

0.0675

AC:

1033

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0778

AC:

270

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5180

South Asian (SAS)

AF:

0.0232

AC:

112

AN:

4828

European-Finnish (FIN)

AF:

0.0776

AC:

824

AN:

10614

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8466

AN:

67994

Other (OTH)

AF:

0.0829

AC:

175

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

563

1126

1690

2253

2816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.107

Hom.:

316

Bravo

AF:

0.0755

TwinsUK

AF:

0.116

AC:

430

ALSPAC

AF:

0.130

AC:

501

ESP6500AA

AF:

0.0268

AC:

118

ESP6500EA

AF:

0.123

AC:

1056

ExAC

AF:

0.0814

AC:

9886

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.118

EpiControl

AF:

0.120

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Primary ciliary dyskinesia (2)

not provided (1)

Primary ciliary dyskinesia 11 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.24

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.0050

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

-0.62

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.60

REVEL

Benign

0.032

Sift

Benign

0.086

Sift4G

Benign

0.33

Polyphen

0.0040

Vest4

0.043

MutPred

0.042

Gain of phosphorylation at T149 (P = 0.0892)

MPC

0.13

ClinPred

0.0028

GERP RS

2.8

PromoterAI

0.057

Neutral

(source)

Varity_R

0.035

gMVP

0.065

Mutation Taster

=96/4

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