Variant rs41267753 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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:

RSPH3 (HGNC:):

RSPH3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
RSPH3	NM_031924.8 linkuse as main transcript	c.211C>T	p.Arg71Trp	missense_variant	3/8	ENST00000367069.7	NP_114130.4	Q86UC2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH3	ENST00000367069.7 linkuse as main transcript	c.211C>T	p.Arg71Trp	missense_variant	3/8	1	NM_031924.8	ENSP00000356036.1		A0A0C4DFU3
RSPH3	ENST00000449822.5 linkuse as main transcript	c.205-3727C>T		intron_variant		2		ENSP00000393195.1		A0A0C4DG29

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

GnomAD3 exomes

AF:

0.0293

AC:

7280

AN:

248750

Hom.:

212

AF XY:

0.0278

AC XY:

3746

AN XY:

134562

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 SAS exome

AF:

0.0230

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

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.0162

Gnomad4 ASJ exome

AF:

0.0127

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0227

Gnomad4 FIN exome

AF:

0.0363

Gnomad4 NFE exome

AF:

0.0241

Gnomad4 OTH exome

AF:

0.0334

GnomAD4 genome

AF:

0.0534

AC:

8132

AN:

152212

Hom.:

380

Cov.:

AF XY:

0.0512

AC XY:

3807

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.0264

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0224

Gnomad4 FIN

AF:

0.0335

Gnomad4 NFE

AF:

0.0247

Gnomad4 OTH

AF:

0.0497

Alfa

AF:

0.0271

Hom.:

157

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 17, 2018

- -

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over