rs147256615

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_001346418.1(RSPH3):​c.44T>G​(p.Leu15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000962 in 1,610,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L15F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

RSPH3
NM_001346418.1 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.05

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]
TAGAP-AS1 (HGNC:55239): (TAGAP antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.00435555).
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000552 (84/152170) while in subpopulation AFR AF = 0.00178 (74/41534). AF 95% confidence interval is 0.00146. There are 0 homozygotes in GnomAd4. There are 33 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346418.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RSPH3
NM_031924.8
MANE Select
c.-383T>G
5_prime_UTR
Exon 1 of 8NP_114130.4
RSPH3
NM_001346418.1
c.44T>Gp.Leu15Arg
missense
Exon 1 of 6NP_001333347.1Q86UC2-2
RSPH3
NR_144434.1
n.255T>G
non_coding_transcript_exon
Exon 1 of 9

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RSPH3
ENST00000367069.7
TSL:1 MANE Select
c.-383T>G
5_prime_UTR
Exon 1 of 8ENSP00000356036.1A0A0C4DFU3
RSPH3
ENST00000884885.1
c.-383T>G
5_prime_UTR
Exon 1 of 7ENSP00000554944.1
TAGAP-AS1
ENST00000664321.2
n.21A>C
non_coding_transcript_exon
Exon 1 of 3

Frequencies

GnomAD3 genomes
AF:
0.000533
AC:
81
AN:
152052
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00171
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000524
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD2 exomes
AF:
0.000127
AC:
31
AN:
243764
AF XY:
0.0000602
show subpopulations
Gnomad AFR exome
AF:
0.00170
Gnomad AMR exome
AF:
0.000146
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000487
AC:
71
AN:
1458378
Hom.:
0
Cov.:
32
AF XY:
0.0000483
AC XY:
35
AN XY:
725332
show subpopulations
African (AFR)
AF:
0.00155
AC:
52
AN:
33442
American (AMR)
AF:
0.000203
AC:
9
AN:
44440
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25902
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39664
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85980
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52496
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5756
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1110426
Other (OTH)
AF:
0.000166
AC:
10
AN:
60272
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
5
10
16
21
26
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<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:
0.000552
AC:
84
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.000443
AC XY:
33
AN XY:
74424
show subpopulations
African (AFR)
AF:
0.00178
AC:
74
AN:
41534
American (AMR)
AF:
0.000523
AC:
8
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5150
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10600
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67982
Other (OTH)
AF:
0.000473
AC:
1
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.528
Heterozygous variant carriers
0
6
11
17
22
28
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000244
Hom.:
1
Bravo
AF:
0.000604
ESP6500AA
AF:
0.000460
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000165
AC:
20

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
Primary ciliary dyskinesia 32 (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.052
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
0.34
DANN
Benign
0.79
DEOGEN2
Benign
0.0023
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.34
T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.0044
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L
PhyloP100
-1.0
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.37
N
REVEL
Benign
0.0090
Sift
Benign
0.039
D
Sift4G
Uncertain
0.030
D
Polyphen
0.0010
B
Vest4
0.10
MVP
0.040
MPC
0.43
ClinPred
0.030
T
GERP RS
-6.3
PromoterAI
-0.0047
Neutral
Varity_R
0.18
gMVP
0.033
Mutation Taster
=96/4
polymorphism

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

Other links and lift over

dbSNP: rs147256615; hg19: chr6-159420965; API
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.