Genetic Variant NM_031924.8:c.204+60G>A (chr6-158993779-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+60G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 889,040 control chromosomes in the GnomAD database, including 10,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1725 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9052 hom. )

Consequence

RSPH3
NM_031924.8 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.546

Publications

5 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:

Genome browser will be placed here

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=-0.83).

BP6

Variant 6-158993779-C-T is Benign according to our data. Variant chr6-158993779-C-T is described in ClinVar as Benign. ClinVar VariationId is 1236074.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.

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+60G>A	intron	N/A	NP_114130.4
RSPH3	NM_001346418.1		c.630+60G>A	intron	N/A	NP_001333347.1	Q86UC2-2
RSPH3	NR_144434.1		n.841+60G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RSPH3	ENST00000367069.7	TSL:1 MANE Select	c.204+60G>A	intron	N/A	ENSP00000356036.1	A0A0C4DFU3
RSPH3	ENST00000884885.1		c.204+60G>A	intron	N/A	ENSP00000554944.1
RSPH3	ENST00000449822.6	TSL:2	c.204+60G>A	intron	N/A	ENSP00000393195.1	A0A0C4DG29

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17346

AN:

152060

Hom.:

1714

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0751

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.0914

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0758

Gnomad OTH

AF:

0.125

GnomAD4 exome

AF:

0.109

AC:

80567

AN:

736862

Hom.:

9052

AF XY:

0.109

AC XY:

42065

AN XY:

387554

show subpopulations

African (AFR)

AF:

0.0608

AC:

1128

AN:

18542

American (AMR)

AF:

0.415

AC:

13042

AN:

31446

Ashkenazi Jewish (ASJ)

AF:

0.0973

AC:

1918

AN:

19714

East Asian (EAS)

AF:

0.462

AC:

15038

AN:

32518

South Asian (SAS)

AF:

0.149

AC:

8199

AN:

55140

European-Finnish (FIN)

AF:

0.0855

AC:

4302

AN:

50320

Middle Eastern (MID)

AF:

0.101

AC:

436

AN:

4298

European-Non Finnish (NFE)

AF:

0.0668

AC:

32684

AN:

489506

Other (OTH)

AF:

0.108

AC:

3820

AN:

35378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

2629

5259

7888

10518

13147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

942

1884

2826

3768

4710

<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:

0.114

AC:

17392

AN:

152178

Hom.:

1725

Cov.:

AF XY:

0.120

AC XY:

8937

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0756

AC:

3138

AN:

41532

American (AMR)

AF:

0.282

AC:

4313

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

376

AN:

3472

East Asian (EAS)

AF:

0.416

AC:

2153

AN:

5180

South Asian (SAS)

AF:

0.194

AC:

936

AN:

4822

European-Finnish (FIN)

AF:

0.0914

AC:

967

AN:

10580

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0758

AC:

5157

AN:

67996

Other (OTH)

AF:

0.130

AC:

275

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

705

1409

2114

2818

3523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.0336

Hom.:

Bravo

AF:

0.133

Asia WGS

AF:

0.281

AC:

978

AN:

3478

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

-0.83

CADD

Benign

0.72

(source)

DANN

Benign

0.71

PhyloP100

-0.55

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over