Variant 6-158986383-C-T 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.243G>A(p.Arg81=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,613,380 control chromosomes in the GnomAD database, including 907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 251 hom., cov: 32)

Exomes 𝑓: 0.026 ( 656 hom. )

Consequence

RSPH3
NM_031924.8 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.368

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=-0.67).

BP6

Variant 6-158986383-C-T is Benign according to our data. Variant chr6-158986383-C-T is described in ClinVar as [Benign]. Clinvar id is 475837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.368 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0992 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.243G>A	p.Arg81=	synonymous_variant	3/8	ENST00000367069.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPH3	ENST00000367069.7 linkuse as main transcript	c.243G>A	p.Arg81=	synonymous_variant	3/8	1	NM_031924.8	P1
RSPH3	ENST00000449822.5 linkuse as main transcript	c.205-3695G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0451

AC:

6855

AN:

152156

Hom.:

250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0239

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0222

Gnomad FIN

AF:

0.0333

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0244

Gnomad OTH

AF:

0.0450

GnomAD3 exomes

AF:

0.0270

AC:

6793

AN:

251358

Hom.:

153

AF XY:

0.0262

AC XY:

3562

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.0993

Gnomad AMR exome

AF:

0.0132

Gnomad ASJ exome

AF:

0.0130

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0228

Gnomad FIN exome

AF:

0.0365

Gnomad NFE exome

AF:

0.0257

Gnomad OTH exome

AF:

0.0289

GnomAD4 exome

AF:

0.0255

AC:

37262

AN:

1461106

Hom.:

656

Cov.:

AF XY:

0.0252

AC XY:

18352

AN XY:

726884

show subpopulations

Gnomad4 AFR exome

AF:

0.100

Gnomad4 AMR exome

AF:

0.0146

Gnomad4 ASJ exome

AF:

0.0128

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0224

Gnomad4 FIN exome

AF:

0.0362

Gnomad4 NFE exome

AF:

0.0242

Gnomad4 OTH exome

AF:

0.0315

GnomAD4 genome

AF:

0.0451

AC:

6873

AN:

152274

Hom.:

251

Cov.:

AF XY:

0.0432

AC XY:

3217

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0238

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0220

Gnomad4 FIN

AF:

0.0333

Gnomad4 NFE

AF:

0.0244

Gnomad4 OTH

AF:

0.0445

Alfa

AF:

0.0278

Hom.:

Bravo

AF:

0.0469

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0245

EpiControl

AF:

0.0237

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

Dec 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.8

DANN

Benign

0.52

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