RSPH3 p.Gly413Arg

Variant names:

• chr6-158977558-C-G
• NM_031924.8:c.1237G>C
• RSPH3 p.Gly413Arg

Your query was ambiguous. Multiple possible variants found:

• chr6-158977558-C-G
• chr6-158977558-C-T
• chr6-158977556-CCC-ACG
• chr6-158977556-CCC-GCG
• chr6-158977556-CCC-TCG
• chr6-158977556-CCC-TCT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031924.8(RSPH3):​c.1237G>C​(p.Gly413Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RSPH3 NM_031924.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 32

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055378288).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH3	NM_031924.8	MANE Select	c.1237G>C	p.Gly413Arg	missense	Exon 8 of 8	NP_114130.4
	RSPH3	NM_001346418.1		c.1375G>C	p.Gly459Arg	missense	Exon 6 of 6	NP_001333347.1	Q86UC2-2
	RSPH3	NR_144434.1		n.1874G>C		non_coding_transcript_exon	Exon 8 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH3	ENST00000367069.7	TSL:1 MANE Select	c.1237G>C	p.Gly413Arg	missense	Exon 8 of 8	ENSP00000356036.1	A0A0C4DFU3
	RSPH3	ENST00000884885.1		c.1069G>C	p.Gly357Arg	missense	Exon 7 of 7	ENSP00000554944.1
	RSPH3	ENST00000449822.6	TSL:2	c.949G>C	p.Gly317Arg	missense	Exon 6 of 6	ENSP00000393195.1	A0A0C4DG29

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.0
DANN	Benign	0.90
DEOGEN2	Benign	0.036	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.66
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.055
Sift	Benign	0.063	T
Sift4G	Benign	0.39	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.025
Mutation Taster		=97/3	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-159398590;