6-43666530-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_152732.5(RSPH9):​c.671-4259C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,522,248 control chromosomes in the GnomAD database, including 584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (42 hom., cov: 32)
  • Exomes 𝑓: 0.026 (542 hom.)
• Consequence: RSPH9 NM_152732.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.01

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 6-43666530-C-T is Benign according to our data. Variant chr6-43666530-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 165064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-43666530-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0182 (2764/152248) while in subpopulation SAS AF= 0.033 (159/4822). AF 95% confidence interval is 0.0288. There are 42 homozygotes in gnomad4. There are 1265 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH9	NM_152732.5	c.671-4259C>T		intron_variant	Intron 4 of 4	ENST00000372163.5	NP_689945.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPH9	ENST00000372163.5	c.671-4259C>T		intron_variant	Intron 4 of 4	1	NM_152732.5	ENSP00000361236.4
RSPH9	ENST00000372165.8	c.722+10C>T		intron_variant	Intron 5 of 5	2		ENSP00000361238.4

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2765 AN: 152132 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.00514

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0288

Gnomad OTH AF: 0.0187

GnomAD3 exomes AF: 0.0193 AC: 2802 AN: 145468 Hom.: 40 AF XY: 0.0202 AC XY: 1582 AN XY: 78424

Gnomad AFR exome AF: 0.00416

Gnomad AMR exome AF: 0.0162

Gnomad ASJ exome AF: 0.00853

Gnomad EAS exome AF: 0.00197

Gnomad SAS exome AF: 0.0296

Gnomad FIN exome AF: 0.00383

Gnomad NFE exome AF: 0.0282

Gnomad OTH exome AF: 0.0192

GnomAD4 exome AF: 0.0262 AC: 35860 AN: 1370000 Hom.: 542 Cov.: 24 AF XY: 0.0262 AC XY: 17713 AN XY: 677188

Gnomad4 AFR exome AF: 0.00436

Gnomad4 AMR exome AF: 0.0165

Gnomad4 ASJ exome AF: 0.00893

Gnomad4 EAS exome AF: 0.000760

Gnomad4 SAS exome AF: 0.0287

Gnomad4 FIN exome AF: 0.00591

Gnomad4 NFE exome AF: 0.0294

Gnomad4 OTH exome AF: 0.0237

GnomAD4 genome AF: 0.0182 AC: 2764 AN: 152248 Hom.: 42 Cov.: 32 AF XY: 0.0170 AC XY: 1265 AN XY: 74442

Gnomad4 AFR AF: 0.00510

Gnomad4 AMR AF: 0.0186

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.0330

Gnomad4 FIN AF: 0.00424

Gnomad4 NFE AF: 0.0288

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0226 Hom.: 18

Bravo AF: 0.0177

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 06, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

722+10C>T in intron 5 of RSPH9: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 4.5% (8/178) of English and Scottish chromosomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih.gov /projects/SNP; dbSNP rs41281830). -

Primary ciliary dyskinesia 12 Benign:1

Nov 04, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.21
DANN	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs41281830; hg19: chr6-43634267;