6-158986383-C-T

Variant names:

• chr6-158986383-C-T
• rs34725942
• NM_031924.8:c.243G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_031924.8(RSPH3):​c.243G>A​(p.Arg81Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,613,380 control chromosomes in the GnomAD database, including 907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (251 hom., cov: 32)
  • Exomes 𝑓: 0.026 (656 hom.)
• Consequence: RSPH3 NM_031924.8 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.368
• Publications: 2 publications found

Genes affected

RSPH3 (HGNC:21054): (radial spoke head 3) The protein encoded by this gene acts as a protein kinase A anchoring protein. Mutations in this gene cause primary ciliary dyskinesia; a disorder characterized by defects of the axoneme in motile cilia and sperm flagella. The homolog of this gene was first identified in the blue-green algae Chlamydomonas as encoding a radial spoke protein that formed a structural component of motile cilia and flagella. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2016]

RSPH3 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 32

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 6-158986383-C-T is Benign according to our data. Variant chr6-158986383-C-T is described in ClinVar as Benign. ClinVar VariationId is 475837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.368 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH3	NM_031924.8	c.243G>A	p.Arg81Arg	synonymous_variant	Exon 3 of 8	ENST00000367069.7	NP_114130.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPH3	ENST00000367069.7	c.243G>A	p.Arg81Arg	synonymous_variant	Exon 3 of 8	1	NM_031924.8	ENSP00000356036.1
RSPH3	ENST00000449822.6	c.205-3695G>A		intron_variant	Intron 2 of 5	2		ENSP00000393195.1

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6855 AN: 152156 Hom.: 250 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0244

Gnomad OTH AF: 0.0450

GnomAD2 exomes AF: 0.0270 AC: 6793 AN: 251358 AF XY: 0.0262

Gnomad AFR exome AF: 0.0993

Gnomad AMR exome AF: 0.0132

Gnomad ASJ exome AF: 0.0130

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.0365

Gnomad NFE exome AF: 0.0257

Gnomad OTH exome AF: 0.0289

GnomAD4 exome AF: 0.0255 AC: 37262 AN: 1461106 Hom.: 656 Cov.: 30 AF XY: 0.0252 AC XY: 18352 AN XY: 726884

African (AFR) AF: 0.100 AC: 3358 AN: 33432

American (AMR) AF: 0.0146 AC: 651 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0128 AC: 334 AN: 26132

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39694

South Asian (SAS) AF: 0.0224 AC: 1936 AN: 86242

European-Finnish (FIN) AF: 0.0362 AC: 1936 AN: 53418

Middle Eastern (MID) AF: 0.0340 AC: 196 AN: 5768

European-Non Finnish (NFE) AF: 0.0242 AC: 26942 AN: 1111338

Other (OTH) AF: 0.0315 AC: 1899 AN: 60360

GnomAD4 genome AF: 0.0451 AC: 6873 AN: 152274 Hom.: 251 Cov.: 32 AF XY: 0.0432 AC XY: 3217 AN XY: 74450

African (AFR) AF: 0.102 AC: 4227 AN: 41544

American (AMR) AF: 0.0238 AC: 364 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0220 AC: 106 AN: 4824

European-Finnish (FIN) AF: 0.0333 AC: 353 AN: 10610

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0244 AC: 1661 AN: 68014

Other (OTH) AF: 0.0445 AC: 94 AN: 2110

Alfa AF: 0.0291 Hom.: 60

Bravo AF: 0.0469

Asia WGS AF: 0.0190 AC: 65 AN: 3478

EpiCase AF: 0.0245

EpiControl AF: 0.0237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 32 Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Dec 17, 2018

GeneDx

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	-0.67
CADD	Benign	3.8
DANN	Benign	0.52
PhyloP100		0.37
Mutation Taster		=100/0	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: rs34725942; hg19: chr6-159407415;