Genetic Variant RSPH3:c.204+263G>A (chr6-158993576-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_031924.8(RSPH3):c.204+263G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 151,856 control chromosomes in the GnomAD database, including 2,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 2281 hom., cov: 31)

Consequence

RSPH3
NM_031924.8 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.68

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 6-158993576-C-T is Benign according to our data. Variant chr6-158993576-C-T is described in ClinVar as Benign. ClinVar VariationId is 1277426.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031924.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RSPH3	NM_031924.8	MANE Select	c.204+263G>A	intron	N/A	NP_114130.4
RSPH3	NM_001346418.1		c.630+263G>A	intron	N/A	NP_001333347.1	Q86UC2-2
RSPH3	NR_144434.1		n.841+263G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RSPH3	ENST00000367069.7	TSL:1 MANE Select	c.204+263G>A	intron	N/A	ENSP00000356036.1	A0A0C4DFU3
RSPH3	ENST00000884885.1		c.204+263G>A	intron	N/A	ENSP00000554944.1
RSPH3	ENST00000449822.6	TSL:2	c.204+263G>A	intron	N/A	ENSP00000393195.1	A0A0C4DG29

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16892

AN:

151738

Hom.:

2272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0467

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0335

Gnomad FIN

AF:

0.0339

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.0263

Gnomad OTH

AF:

0.0987

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.111

AC:

16929

AN:

151856

Hom.:

2281

Cov.:

AF XY:

0.109

AC XY:

8063

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.330

AC:

13631

AN:

41304

American (AMR)

AF:

0.0466

AC:

711

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3466

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.0329

AC:

158

AN:

4800

European-Finnish (FIN)

AF:

0.0339

AC:

357

AN:

10544

Middle Eastern (MID)

AF:

0.0616

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0263

AC:

1786

AN:

67984

Other (OTH)

AF:

0.0972

AC:

205

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

620

1240

1860

2480

3100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0608

Hom.:

211

Bravo

AF:

0.123

Asia WGS

AF:

0.0390

AC:

135

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0080

(source)

DANN

Benign

0.54

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over