rs150432556

Variant names:

• chr6-158977689-C-A
• NM_031924.8:c.1106G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-158977689-C-A
• chr6-158977689-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031924.8(RSPH3):​c.1106G>T​(p.Arg369Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R369Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RSPH3 NM_031924.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.698

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08702338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH3	NM_031924.8	c.1106G>T	p.Arg369Leu	missense_variant	Exon 8 of 8	ENST00000367069.7	NP_114130.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPH3	ENST00000367069.7	c.1106G>T	p.Arg369Leu	missense_variant	Exon 8 of 8	1	NM_031924.8	ENSP00000356036.1
RSPH3	ENST00000449822.5	c.818G>T	p.Arg273Leu	missense_variant	Exon 6 of 6	2		ENSP00000393195.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.026	T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.53	T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.087	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	.;.;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.048
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.023	D;D;D
Polyphen		0.039	.;.;B
Vest4		0.15
MutPred		0.23		.;.;Loss of solvent accessibility (P = 0.0606);
MVP		0.17
MPC		0.36
ClinPred		0.12	T
GERP RS		1.5
Varity_R		0.070
gMVP		0.065

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-159398721;