Variant rs10945587 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 ENST00000367069.7(RSPH3):c.9A>G(p.Ser3=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,598,204 control chromosomes in the GnomAD database, including 31,328 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S3S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.24 ( 5731 hom., cov: 31)

Exomes 𝑓: 0.16 ( 25597 hom. )

Consequence

RSPH3
ENST00000367069.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.161

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:

TAGAP-AS1 (HGNC:55239): (TAGAP antisense RNA 1)

TAGAP-AS1 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=-0.93).

BP6

Variant 6-158999542-T-C is Benign according to our data. Variant chr6-158999542-T-C is described in ClinVar as [Benign]. Clinvar id is 1165004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.161 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.9A>G	p.Ser3=	synonymous_variant	1/8	ENST00000367069.7	NP_114130.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RSPH3	ENST00000367069.7 linkuse as main transcript	c.9A>G	p.Ser3=	synonymous_variant	1/8	1	NM_031924.8	ENSP00000356036	P1
RSPH3	ENST00000449822.5 linkuse as main transcript	c.9A>G	p.Ser3=	synonymous_variant	1/6	2		ENSP00000393195
TAGAP-AS1	ENST00000607391.5 linkuse as main transcript	n.236+8970T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36150

AN:

151238

Hom.:

5704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.402

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.237

GnomAD3 exomes

AF:

0.232

AC:

56530

AN:

243884

Hom.:

9627

AF XY:

0.215

AC XY:

28243

AN XY:

131498

show subpopulations

Gnomad AFR exome

AF:

0.404

Gnomad AMR exome

AF:

0.513

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.403

Gnomad SAS exome

AF:

0.210

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.127

Gnomad OTH exome

AF:

0.196

GnomAD4 exome

AF:

0.160

AC:

231640

AN:

1446848

Hom.:

25597

Cov.:

AF XY:

0.159

AC XY:

113979

AN XY:

717354

show subpopulations

Gnomad4 AFR exome

AF:

0.402

Gnomad4 AMR exome

AF:

0.498

Gnomad4 ASJ exome

AF:

0.126

Gnomad4 EAS exome

AF:

0.465

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.140

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.181

GnomAD4 genome

AF:

0.239

AC:

36237

AN:

151356

Hom.:

5731

Cov.:

AF XY:

0.242

AC XY:

17905

AN XY:

73942

show subpopulations

Gnomad4 AFR

AF:

0.402

Gnomad4 AMR

AF:

0.353

Gnomad4 ASJ

AF:

0.127

Gnomad4 EAS

AF:

0.415

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.140

Gnomad4 NFE

AF:

0.125

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.154

Hom.:

1341

Bravo

AF:

0.268

Asia WGS

AF:

0.323

AC:

1121

AN:

3478

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

-0.93

CADD

Benign

5.7

DANN

Benign

0.50

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