rs760134926

Positions:

• chr6-43650477-A-C
• chr6-43650477-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152732.5(RSPH9):​c.330A>C​(p.Glu110Asp) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RSPH9 NM_152732.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.704

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]

POLR1C (HGNC:20194): (RNA polymerase I and III subunit C) The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

RSPH9 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29963344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH9	NM_152732.5	c.330A>C	p.Glu110Asp	missense_variant	2/5	ENST00000372163.5	NP_689945.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH9	ENST00000372163.5	c.330A>C	p.Glu110Asp	missense_variant	2/5	1	NM_152732.5	ENSP00000361236.4
RSPH9	ENST00000372165.8	c.330A>C	p.Glu110Asp	missense_variant	2/6	2		ENSP00000361238.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.21
Sift	Benign	0.044	D;D
Sift4G	Uncertain	0.036	D;D
Polyphen		0.92	.;P
Vest4		0.38
MutPred		0.36		Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);
MVP		0.61
MPC		0.086
ClinPred		0.88	D
GERP RS		2.5
Varity_R		0.13
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs760134926; hg19: chr6-43618214;