Variant chr6-158993811-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_031924.8(RSPH3):c.204+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,230,980 control chromosomes in the GnomAD database, including 13,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1713 hom., cov: 32)

Exomes 𝑓: 0.10 ( 11876 hom. )

Consequence

RSPH3
NM_031924.8 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.564

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-158993811-G-A is Benign according to our data. Variant chr6-158993811-G-A is described in ClinVar as [Benign]. Clinvar id is 1289448.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 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.204+28C>T		intron_variant		ENST00000367069.7	NP_114130.4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
RSPH3	ENST00000367069.7 linkuse as main transcript	c.204+28C>T	intron_variant	1	NM_031924.8	ENSP00000356036	P1
RSPH3	ENST00000449822.5 linkuse as main transcript	c.204+28C>T	intron_variant	2		ENSP00000393195
TAGAP-AS1	ENST00000607391.5 linkuse as main transcript	n.236+3239G>A	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17151

AN:

151962

Hom.:

1702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0704

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.0913

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0759

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.160

AC:

37863

AN:

236668

Hom.:

5713

AF XY:

0.150

AC XY:

19196

AN XY:

128350

show subpopulations

Gnomad AFR exome

AF:

0.0644

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.389

Gnomad SAS exome

AF:

0.167

Gnomad FIN exome

AF:

0.0858

Gnomad NFE exome

AF:

0.0769

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.104

AC:

112537

AN:

1078896

Hom.:

11876

Cov.:

AF XY:

0.105

AC XY:

57868

AN XY:

552666

show subpopulations

Gnomad4 AFR exome

AF:

0.0587

Gnomad4 AMR exome

AF:

0.440

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.460

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.0872

Gnomad4 NFE exome

AF:

0.0676

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.113

AC:

17197

AN:

152084

Hom.:

1713

Cov.:

AF XY:

0.119

AC XY:

8846

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0709

Gnomad4 AMR

AF:

0.283

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.416

Gnomad4 SAS

AF:

0.195

Gnomad4 FIN

AF:

0.0913

Gnomad4 NFE

AF:

0.0759

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.0938

Hom.:

195

Bravo

AF:

0.131

Asia WGS

AF:

0.281

AC:

978

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.89

CADD

Benign

0.31

DANN

Benign

0.63

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