rs1351239709

Variant names:

• chr6-43655649-A-C
• NM_152732.5:c.481A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-43655649-A-C
• chr6-43655649-A-G

Variant summary

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

The NM_152732.5(RSPH9):​c.481A>C​(p.Lys161Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RSPH9 NM_152732.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.90

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH9	NM_152732.5	c.481A>C	p.Lys161Gln	missense_variant	Exon 3 of 5	ENST00000372163.5	NP_689945.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPH9	ENST00000372163.5	c.481A>C	p.Lys161Gln	missense_variant	Exon 3 of 5	1	NM_152732.5	ENSP00000361236.4
RSPH9	ENST00000372165.8	c.436A>C	p.Lys146Gln	missense_variant	Exon 3 of 6	2		ENSP00000361238.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.4	.;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.5	D;N
REVEL	Benign	0.18
Sift	Benign	0.049	D;T
Sift4G	Benign	0.086	T;T
Polyphen		0.97	.;D
Vest4		0.62
MutPred		0.49		.;Loss of methylation at K161 (P = 0.0067);
MVP		0.65
MPC		0.31
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.19
gMVP		0.71

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: chr6-43623386;