rs41281830

Variant names:

• chr6-43666530-C-A
• rs41281830
• NM_152732.5:c.671-4259C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-43666530-C-A
• chr6-43666530-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152732.5(RSPH9):​c.671-4259C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,370,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: RSPH9 NM_152732.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• 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: ClinGen, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

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.671-4259C>A		intron	N/A	NP_689945.2
	RSPH9	NM_001424119.1		c.767+10C>A		intron	N/A	NP_001411048.1
	RSPH9	NM_001193341.2		c.722+10C>A		intron	N/A	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.671-4259C>A		intron	N/A	ENSP00000361236.4	Q9H1X1-1
	RSPH9	ENST00000372165.8	TSL:2	c.722+10C>A		intron	N/A	ENSP00000361238.4	Q9H1X1-2
	RSPH9	ENST00000890744.1		c.671-4259C>A		intron	N/A	ENSP00000560803.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1370264 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 677312

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30962

American (AMR) AF: 0.00 AC: 0 AN: 35136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24754

East Asian (EAS) AF: 0.00 AC: 0 AN: 35526

South Asian (SAS) AF: 0.00 AC: 0 AN: 78290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5528

European-Non Finnish (NFE) AF: 9.48e-7 AC: 1 AN: 1055116

Other (OTH) AF: 0.00 AC: 0 AN: 56898

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.081
DANN	Benign	0.47
PhyloP100		-2.0

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

Other links and lift over

dbSNP: rs41281830; hg19: chr6-43634267;