rs727503395

chr6-43670942-TG-AT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_152732.5(RSPH9):c.824_825delinsAT(p.Met275Asn) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M275I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RSPH9 NM_152732.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.27

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSPH9	NM_152732.5	c.824_825delinsAT	p.Met275Asn	missense_variant	5/5	ENST00000372163.5
RSPH9	NM_001193341.2	c.876_877delinsAT	p.His292_Ala293delinsGlnSer	missense_variant	6/6
POLR1C	NM_001318876.2	c.945+141671_945+141672delinsAT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPH9	ENST00000372163.5	c.824_825delinsAT	p.Met275Asn	missense_variant	5/5	1	NM_152732.5	P1
RSPH9	ENST00000372165.8	c.876_877delinsAT	p.His292_Ala293delinsGlnSer	missense_variant	6/6	2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Oct 30, 2013

The His292_Ala293delinsGlnSer variant in RSPH9 has not been reported in individu als with pulmonary disease or in large population studies. This variant changes two adjacent bases leading to a replacement of Histidine (His) and Alanine (Ala) at positions 292-293 with Glutamine (Gln) and Serine (Ser).Computational analys es (biochemical amino acid properties, evolutionary conservation, AlignGVGD, Pol yPhen2, and SIFT) do not provide strong support for or against an impact to the protein based on either amino acid change. Of note, neither the His292Gln nor th e Ala293Ser variants have independently been reported in individuals with pulmon ary disease or in large population studies. In summary, additional studies are n eeded to fully assess the clinical significance of the His292_Ala293delinsGlnSer variant. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs727503395; hg19: chr6-43638679;