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rs116017511

chr6-158993902-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_031924.8(RSPH3):c.141A>G(p.Gly47=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,608,162 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0064 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00074 ( 15 hom. )

Consequence

RSPH3
NM_031924.8 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00500
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)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-158993902-T-C is Benign according to our data. Variant chr6-158993902-T-C is described in ClinVar as [Benign]. Clinvar id is 475834.Status of the report is criteria_provided_single_submitter, 1 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=0.005 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00636 (968/152286) while in subpopulation AFR AF= 0.0221 (917/41550). AF 95% confidence interval is 0.0209. There are 9 homozygotes in gnomad4. There are 456 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RSPH3NM_031924.8 linkuse as main transcriptc.141A>G p.Gly47= synonymous_variant 2/8 ENST00000367069.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RSPH3ENST00000367069.7 linkuse as main transcriptc.141A>G p.Gly47= synonymous_variant 2/81 NM_031924.8 P1
RSPH3ENST00000449822.5 linkuse as main transcriptc.141A>G p.Gly47= synonymous_variant 2/62
TAGAP-AS1ENST00000607391.5 linkuse as main transcriptn.236+3330T>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00635
AC:
966
AN:
152168
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0221
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00190
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:
0.000206
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00173
AC:
435
AN:
251308
Hom.:
3
AF XY:
0.00123
AC XY:
167
AN XY:
135848
show subpopulations
Gnomad AFR exome
AF:
0.0228
Gnomad AMR exome
AF:
0.00110
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000194
Gnomad OTH exome
AF:
0.000815
GnomAD4 exome
AF:
0.000740
AC:
1077
AN:
1455876
Hom.:
15
Cov.:
28
AF XY:
0.000644
AC XY:
467
AN XY:
724614
show subpopulations
Gnomad4 AFR exome
AF:
0.0224
Gnomad4 AMR exome
AF:
0.00130
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000153
Gnomad4 OTH exome
AF:
0.00158
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00636
AC:
968
AN:
152286
Hom.:
9
Cov.:
32
AF XY:
0.00612
AC XY:
456
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0221
Gnomad4 AMR
AF:
0.00190
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00298
Hom.:
4
Bravo
AF:
0.00700
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000356

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 32 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeOct 26, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
7.0
Dann
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs116017511; hg19: chr6-159414934; API