6-43666530-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_152732.5(RSPH9):c.671-4259C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,522,248 control chromosomes in the GnomAD database, including 584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 42 hom., cov: 32)

Exomes 𝑓: 0.026 ( 542 hom. )

Consequence

RSPH9
NM_152732.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.01

Publications

1 publications found

Variant links:

Genes affected

RSPH9 (HGNC:21057): (radial spoke head component 9) This gene encodes a protein thought to be a component of the radial spoke head in motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia 12. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jul 2010]

RSPH9 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 12
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RSPH9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

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

BP6

Variant 6-43666530-C-T is Benign according to our data. Variant chr6-43666530-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 165064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0182 (2764/152248) while in subpopulation SAS AF = 0.033 (159/4822). AF 95% confidence interval is 0.0288. There are 42 homozygotes in GnomAd4. There are 1265 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 42 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH9	NM_152732.5 link	c.671-4259C>T		intron_variant	Intron 4 of 4	ENST00000372163.5	NP_689945.2	Q9H1X1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPH9	ENST00000372163.5 link	c.671-4259C>T		intron_variant	Intron 4 of 4	1	NM_152732.5	ENSP00000361236.4		Q9H1X1-1
RSPH9	ENST00000372165.8 link	c.722+10C>T		intron_variant	Intron 5 of 5	2		ENSP00000361238.4		Q9H1X1-2

Frequencies

GnomAD3 genomes

AF:

0.0182

AC:

2765

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00514

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0187

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.0332

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0288

Gnomad OTH

AF:

0.0187

GnomAD2 exomes

AF:

0.0193

AC:

2802

AN:

145468

AF XY:

0.0202

show subpopulations

Gnomad AFR exome

AF:

0.00416

Gnomad AMR exome

AF:

0.0162

Gnomad ASJ exome

AF:

0.00853

Gnomad EAS exome

AF:

0.00197

Gnomad FIN exome

AF:

0.00383

Gnomad NFE exome

AF:

0.0282

Gnomad OTH exome

AF:

0.0192

GnomAD4 exome

AF:

0.0262

AC:

35860

AN:

1370000

Hom.:

542

Cov.:

AF XY:

0.0262

AC XY:

17713

AN XY:

677188

show subpopulations

African (AFR)

AF:

0.00436

AC:

135

AN:

30962

American (AMR)

AF:

0.0165

AC:

580

AN:

35134

Ashkenazi Jewish (ASJ)

AF:

0.00893

AC:

221

AN:

24754

East Asian (EAS)

AF:

0.000760

AC:

AN:

35526

South Asian (SAS)

AF:

0.0287

AC:

2247

AN:

78276

European-Finnish (FIN)

AF:

0.00591

AC:

284

AN:

48052

Middle Eastern (MID)

AF:

0.00561

AC:

AN:

5528

European-Non Finnish (NFE)

AF:

0.0294

AC:

30988

AN:

1054886

Other (OTH)

AF:

0.0237

AC:

1347

AN:

56882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1603

3205

4808

6410

8013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1156

2312

3468

4624

5780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0182

AC:

2764

AN:

152248

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1265

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00510

AC:

212

AN:

41550

American (AMR)

AF:

0.0186

AC:

285

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3472

East Asian (EAS)

AF:

0.00270

AC:

AN:

5178

South Asian (SAS)

AF:

0.0330

AC:

159

AN:

4822

European-Finnish (FIN)

AF:

0.00424

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0288

AC:

1962

AN:

68012

Other (OTH)

AF:

0.0185

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

141

281

422

562

703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0226

Hom.:

Bravo

AF:

0.0177

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 06, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

722+10C>T in intron 5 of RSPH9: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 4.5% (8/178) of English and Scottish chromosomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih.gov /projects/SNP; dbSNP rs41281830). -

Primary ciliary dyskinesia 12

Benign:1

Nov 04, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.21

(source)

DANN

Benign

0.54

PhyloP100

-2.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over