NM_152732.5:c.798C>G

Variant names:

• chr6-43670916-C-G
• NM_152732.5:c.798C>G
• RSPH9 p.Gly266Gly

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_152732.5(RSPH9):​c.798C>G​(p.Gly266Gly) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G266G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RSPH9 NM_152732.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 0 publications found

Genes affected

RSPH9 (HGNC:21057): (radial spoke head component 9) This gene encodes a protein thought to be a component of the radial spoke head in motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia 12. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jul 2010]

RSPH9 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 12

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027800113).
• BP7: Synonymous conserved (PhyloP=-1.94 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152732.5. 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
	RSPH9	NM_152732.5	MANE Select	c.798C>G	p.Gly266Gly	synonymous	Exon 5 of 5	NP_689945.2
	RSPH9	NM_001424119.1		c.895C>G	p.Arg299Gly	missense	Exon 6 of 6	NP_001411048.1
	RSPH9	NM_001193341.2		c.850C>G	p.Arg284Gly	missense	Exon 6 of 6	NP_001180270.1	Q9H1X1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH9	ENST00000372163.5	TSL:1 MANE Select	c.798C>G	p.Gly266Gly	synonymous	Exon 5 of 5	ENSP00000361236.4	Q9H1X1-1
	RSPH9	ENST00000372165.8	TSL:2	c.850C>G	p.Arg284Gly	missense	Exon 6 of 6	ENSP00000361238.4	Q9H1X1-2
	RSPH9	ENST00000890744.1		c.798C>G	p.Gly266Gly	synonymous	Exon 6 of 6	ENSP00000560803.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.52
DANN	Benign	0.95
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.9
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.027
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
gMVP		0.30
Mutation Taster		=98/2	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: chr6-43638653;