Variant chr6-158977601-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_031924.8(RSPH3):c.1194A>G(p.Glu398=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,290 control chromosomes in the GnomAD database, including 20,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2047 hom., cov: 32)

Exomes 𝑓: 0.13 ( 18425 hom. )

Consequence

RSPH3
NM_031924.8 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.86

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 6-158977601-T-C is Benign according to our data. Variant chr6-158977601-T-C is described in ClinVar as [Benign]. Clinvar id is 1170194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.86 with no splicing effect.

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 linkuse as main transcript	c.1194A>G	p.Glu398=	synonymous_variant	8/8	ENST00000367069.7	NP_114130.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH3	ENST00000367069.7 linkuse as main transcript	c.1194A>G	p.Glu398=	synonymous_variant	8/8	1	NM_031924.8	ENSP00000356036	P1
RSPH3	ENST00000449822.5 linkuse as main transcript	c.906A>G	p.Glu302=	synonymous_variant	6/6	2		ENSP00000393195

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20018

AN:

151974

Hom.:

2037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0842

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0995

Gnomad OTH

AF:

0.141

GnomAD3 exomes

AF:

0.188

AC:

47187

AN:

251182

Hom.:

7492

AF XY:

0.177

AC XY:

23991

AN XY:

135766

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:

187577

AN:

1461198

Hom.:

18425

Cov.:

AF XY:

0.128

AC XY:

93397

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.0791

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:

20067

AN:

152092

Hom.:

2047

Cov.:

AF XY:

0.137

AC XY:

10190

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0847

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:

0.0995

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.119

Hom.:

2543

Bravo

AF:

0.151

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

Jan 31, 2024

- -

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

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.38

DANN

Benign

0.36

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