Menu
GeneBe

6-158977732-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_031924.8(RSPH3):c.1063C>T(p.Leu355=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,613,654 control chromosomes in the GnomAD database, including 16,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1728 hom., cov: 32)
Exomes 𝑓: 0.11 ( 15206 hom. )

Consequence

RSPH3
NM_031924.8 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.541
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-158977732-G-A is Benign according to our data. Variant chr6-158977732-G-A is described in ClinVar as [Benign]. Clinvar id is 1166973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.541 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
RSPH3NM_031924.8 linkuse as main transcriptc.1063C>T p.Leu355= synonymous_variant 8/8 ENST00000367069.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RSPH3ENST00000367069.7 linkuse as main transcriptc.1063C>T p.Leu355= synonymous_variant 8/81 NM_031924.8 P1
RSPH3ENST00000449822.5 linkuse as main transcriptc.775C>T p.Leu259= synonymous_variant 6/62

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.114
AC:
17320
AN:
152016
Hom.:
1717
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0749
Gnomad AMI
AF:
0.0515
Gnomad AMR
AF:
0.282
Gnomad ASJ
AF:
0.108
Gnomad EAS
AF:
0.415
Gnomad SAS
AF:
0.193
Gnomad FIN
AF:
0.0906
Gnomad MID
AF:
0.101
Gnomad NFE
AF:
0.0759
Gnomad OTH
AF:
0.125
GnomAD3 exomes
AF:
0.171
AC:
43071
AN:
251394
Hom.:
6876
AF XY:
0.160
AC XY:
21716
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.0715
Gnomad AMR exome
AF:
0.474
Gnomad ASJ exome
AF:
0.106
Gnomad EAS exome
AF:
0.401
Gnomad SAS exome
AF:
0.176
Gnomad FIN exome
AF:
0.0862
Gnomad NFE exome
AF:
0.0787
Gnomad OTH exome
AF:
0.145
GnomAD4 exome
AF:
0.107
AC:
156115
AN:
1461520
Hom.:
15206
Cov.:
32
AF XY:
0.107
AC XY:
78010
AN XY:
727080
show subpopulations
Gnomad4 AFR exome
AF:
0.0689
Gnomad4 AMR exome
AF:
0.456
Gnomad4 ASJ exome
AF:
0.106
Gnomad4 EAS exome
AF:
0.463
Gnomad4 SAS exome
AF:
0.173
Gnomad4 FIN exome
AF:
0.0887
Gnomad4 NFE exome
AF:
0.0764
Gnomad4 OTH exome
AF:
0.117
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.114
AC:
17367
AN:
152134
Hom.:
1728
Cov.:
32
AF XY:
0.120
AC XY:
8905
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.0754
Gnomad4 AMR
AF:
0.283
Gnomad4 ASJ
AF:
0.108
Gnomad4 EAS
AF:
0.416
Gnomad4 SAS
AF:
0.193
Gnomad4 FIN
AF:
0.0906
Gnomad4 NFE
AF:
0.0759
Gnomad4 OTH
AF:
0.130
Alfa
AF:
0.0854
Hom.:
374
Bravo
AF:
0.133
Asia WGS
AF:
0.282
AC:
981
AN:
3478
EpiCase
AF:
0.0768
EpiControl
AF:
0.0811

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 submitterclinical testingInvitaeJan 31, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxFeb 25, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
Cadd
Benign
0.30
Dann
Benign
0.51

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.

Other links and lift over

dbSNP: rs12191022; hg19: chr6-159398764; COSMIC: COSV51921618; COSMIC: COSV51921618; API