chr6-43645081-A-G

Variant names:

• chr6-43645081-A-G
• rs59110261
• NM_152732.5:c.-18A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152732.5(RSPH9):​c.-18A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00778 in 1,606,496 control chromosomes in the GnomAD database, including 830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (465 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (365 hom.)
• Consequence: RSPH9 NM_152732.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0780
• Publications: 1 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 6-43645081-A-G is Benign according to our data. Variant chr6-43645081-A-G is described in ClinVar as Benign. ClinVar VariationId is 262684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

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.-18A>G		5_prime_UTR	Exon 1 of 5	NP_689945.2
	RSPH9	NM_001424119.1		c.-18A>G		5_prime_UTR	Exon 1 of 6	NP_001411048.1
	RSPH9	NM_001193341.2		c.-18A>G		5_prime_UTR	Exon 1 of 6	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.-18A>G		5_prime_UTR	Exon 1 of 5	ENSP00000361236.4	Q9H1X1-1
	RSPH9	ENST00000372165.8	TSL:2	c.-18A>G		5_prime_UTR	Exon 1 of 6	ENSP00000361238.4	Q9H1X1-2
	RSPH9	ENST00000890744.1		c.-18A>G		5_prime_UTR	Exon 2 of 6	ENSP00000560803.1

Frequencies

GnomAD3 genomes AF: 0.0416 AC: 6331 AN: 152080 Hom.: 463 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0302

GnomAD2 exomes AF: 0.0107 AC: 2554 AN: 239164 AF XY: 0.00788

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.00838

Gnomad ASJ exome AF: 0.000912

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000529

Gnomad NFE exome AF: 0.000468

Gnomad OTH exome AF: 0.00453

GnomAD4 exome AF: 0.00423 AC: 6152 AN: 1454298 Hom.: 365 Cov.: 31 AF XY: 0.00369 AC XY: 2674 AN XY: 723850

African (AFR) AF: 0.143 AC: 4777 AN: 33430

American (AMR) AF: 0.00891 AC: 398 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00146 AC: 38 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86208

European-Finnish (FIN) AF: 0.0000208 AC: 1 AN: 48148

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5764

European-Non Finnish (NFE) AF: 0.000294 AC: 326 AN: 1110066

Other (OTH) AF: 0.00926 AC: 558 AN: 60244

GnomAD4 genome AF: 0.0417 AC: 6345 AN: 152198 Hom.: 465 Cov.: 32 AF XY: 0.0399 AC XY: 2970 AN XY: 74412

African (AFR) AF: 0.144 AC: 5984 AN: 41506

American (AMR) AF: 0.0154 AC: 236 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68002

Other (OTH) AF: 0.0299 AC: 63 AN: 2110

Alfa AF: 0.0172 Hom.: 65

Bravo AF: 0.0471

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia 12 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.74
PhyloP100		0.078
PromoterAI		0.53	Over-expression
Mutation Taster		=300/0	polymorphism (auto)

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: rs59110261; hg19: chr6-43612818;