Variant 6-158977668-C-T 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.1127G>A(p.Gly376Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,430 control chromosomes in the GnomAD database, including 20,467 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2042 hom., cov: 32)

Exomes 𝑓: 0.13 ( 18425 hom. )

Consequence

RSPH3
NM_031924.8 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.887

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.494986E-4).

BP6

Variant 6-158977668-C-T is Benign according to our data. Variant chr6-158977668-C-T is described in ClinVar as [Benign]. Clinvar id is 1170195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH3	NM_031924.8 link	c.1127G>A	p.Gly376Asp	missense_variant	8/8	ENST00000367069.7	NP_114130.4	Q86UC2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH3	ENST00000367069.7 link	c.1127G>A	p.Gly376Asp	missense_variant	8/8	1	NM_031924.8	ENSP00000356036.1		A0A0C4DFU3
RSPH3	ENST00000449822.5 link	c.839G>A	p.Gly280Asp	missense_variant	6/6	2		ENSP00000393195.1		A0A0C4DG29

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20019

AN:

151990

Hom.:

2032

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0844

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0994

Gnomad OTH

AF:

0.140

GnomAD3 exomes

AF:

0.188

AC:

47260

AN:

251352

Hom.:

7496

AF XY:

0.177

AC XY:

24034

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.0804

Gnomad AMR exome

AF:

0.488

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.401

Gnomad SAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.102

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.128

AC:

187607

AN:

1461322

Hom.:

18425

Cov.:

AF XY:

0.129

AC XY:

93424

AN XY:

727026

show subpopulations

Gnomad4 AFR exome

AF:

0.0790

Gnomad4 AMR exome

AF:

0.471

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.463

Gnomad4 SAS exome

AF:

0.186

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.132

AC:

20068

AN:

152108

Hom.:

2042

Cov.:

AF XY:

0.137

AC XY:

10195

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0849

Gnomad4 AMR

AF:

0.306

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.414

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.0994

Gnomad4 OTH

AF:

0.145

Alfa

AF:

0.117

Hom.:

3449

Bravo

AF:

0.151

TwinsUK

AF:

0.0944

AC:

350

ALSPAC

AF:

0.105

AC:

403

ESP6500AA

AF:

0.0917

AC:

404

ESP6500EA

AF:

0.108

AC:

926

ExAC

AF:

0.175

AC:

21297

Asia WGS

AF:

0.287

AC:

998

AN:

3478

EpiCase

AF:

0.102

EpiControl

AF:

0.105

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

Feb 03, 2025

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.4

DANN

Benign

0.085

DEOGEN2

Benign

0.0018

T;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.000070

LIST_S2

Benign

0.33

T;T;T

MetaRNN

Benign

0.00075

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.0

.;.;N

PrimateAI

Benign

0.27

PROVEAN

Benign

1.6

N;N;N

REVEL

Benign

0.058

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.017

MPC

0.38

ClinPred

0.0040

GERP RS

2.8

Varity_R

0.028

gMVP

0.027

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

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