Variant rs144678437 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.1136A>G(p.Gln379Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00325 in 1,614,168 control chromosomes in the GnomAD database, including 171 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 0.0051 ( 17 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 154 hom. )

Consequence

RSPH3
NM_031924.8 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.297

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=0.00335446).

BP6

Variant 6-158977659-T-C is Benign according to our data. Variant chr6-158977659-T-C is described in ClinVar as [Benign]. Clinvar id is 475825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSPH3	NM_031924.8 linkuse as main transcript	c.1136A>G	p.Gln379Arg	missense_variant	8/8	ENST00000367069.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPH3	ENST00000367069.7 linkuse as main transcript	c.1136A>G	p.Gln379Arg	missense_variant	8/8	1	NM_031924.8	P1
RSPH3	ENST00000449822.5 linkuse as main transcript	c.848A>G	p.Gln283Arg	missense_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.00512

AC:

779

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0358

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0112

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.0125

AC:

3150

AN:

251432

Hom.:

131

AF XY:

0.00968

AC XY:

1316

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.0774

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00473

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.0106

Gnomad NFE exome

AF:

0.000554

Gnomad OTH exome

AF:

0.00864

GnomAD4 exome

AF:

0.00306

AC:

4467

AN:

1461858

Hom.:

154

Cov.:

AF XY:

0.00273

AC XY:

1984

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.0733

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.00401

Gnomad4 SAS exome

AF:

0.000487

Gnomad4 FIN exome

AF:

0.0104

Gnomad4 NFE exome

AF:

0.000192

Gnomad4 OTH exome

AF:

0.00273

GnomAD4 genome

AF:

0.00514

AC:

783

AN:

152310

Hom.:

Cov.:

AF XY:

0.00562

AC XY:

419

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.0360

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00290

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0112

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.00766

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00942

AC:

1144

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

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

Invitae

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.9

DANN

Benign

0.92

DEOGEN2

Benign

0.014

T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.42

T;T;T

MetaRNN

Benign

0.0034

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

.;.;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.68

N;N;N

REVEL

Benign

0.0040

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.071

T;D;D

Polyphen

0.0030

.;.;B

Vest4

0.079

MPC

0.32

ClinPred

0.0014

GERP RS

-1.7

Varity_R

0.038

gMVP

0.028

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