21-42477439-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_080860.4(RSPH1):c.579A>G(p.Arg193Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,613,592 control chromosomes in the GnomAD database, including 1,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 92 hom., cov: 34)

Exomes 𝑓: 0.037 ( 1159 hom. )

Consequence

RSPH1
NM_080860.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.08

Variant links:

Genes affected

RSPH1 (HGNC:12371): (radial spoke head component 1) This gene encodes a male meiotic metaphase chromosome-associated acidic protein. This gene is expressed in tissues with motile cilia or flagella, including the trachea, lungs, airway brushings, and testes. Mutations in this gene result in primary ciliary dyskinesia-24. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

RSPH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 21-42477439-T-C is Benign according to our data. Variant chr21-42477439-T-C is described in ClinVar as [Benign]. Clinvar id is 227051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.09 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0296 (4515/152390) while in subpopulation NFE AF= 0.0415 (2822/68030). AF 95% confidence interval is 0.0402. There are 92 homozygotes in gnomad4. There are 2265 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 92 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH1	NM_080860.4 link	c.579A>G	p.Arg193Arg	synonymous_variant	Exon 7 of 9	ENST00000291536.8	NP_543136.1	Q8WYR4-1
RSPH1	NM_001286506.2 link	c.465A>G	p.Arg155Arg	synonymous_variant	Exon 6 of 8		NP_001273435.1	Q8WYR4-2
RSPH1	XM_011529786.2 link	c.507A>G	p.Arg169Arg	synonymous_variant	Exon 6 of 8		XP_011528088.1
RSPH1	XM_005261208.3 link	c.372A>G	p.Arg124Arg	synonymous_variant	Exon 5 of 7		XP_005261265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RSPH1	ENST00000291536.8 link	c.579A>G	p.Arg193Arg	synonymous_variant	Exon 7 of 9	1	NM_080860.4	ENSP00000291536.3	Q8WYR4-1
RSPH1	ENST00000398352.3 link	c.465A>G	p.Arg155Arg	synonymous_variant	Exon 6 of 8	5		ENSP00000381395.3	Q8WYR4-2
RSPH1	ENST00000493019.1 link	n.2197A>G		non_coding_transcript_exon_variant	Exon 6 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.0297

AC:

4520

AN:

152272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00694

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0224

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0329

Gnomad FIN

AF:

0.0533

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0415

Gnomad OTH

AF:

0.0339

GnomAD3 exomes

AF:

0.0336

AC:

8435

AN:

251312

Hom.:

210

AF XY:

0.0356

AC XY:

4835

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00622

Gnomad AMR exome

AF:

0.0176

Gnomad ASJ exome

AF:

0.0613

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0419

Gnomad FIN exome

AF:

0.0501

Gnomad NFE exome

AF:

0.0397

Gnomad OTH exome

AF:

0.0365

GnomAD4 exome

AF:

0.0369

AC:

53934

AN:

1461202

Hom.:

1159

Cov.:

AF XY:

0.0375

AC XY:

27274

AN XY:

726916

show subpopulations

Gnomad4 AFR exome

AF:

0.00535

Gnomad4 AMR exome

AF:

0.0187

Gnomad4 ASJ exome

AF:

0.0615

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0411

Gnomad4 FIN exome

AF:

0.0483

Gnomad4 NFE exome

AF:

0.0385

Gnomad4 OTH exome

AF:

0.0366

GnomAD4 genome

AF:

0.0296

AC:

4515

AN:

152390

Hom.:

Cov.:

AF XY:

0.0304

AC XY:

2265

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.00690

Gnomad4 AMR

AF:

0.0223

Gnomad4 ASJ

AF:

0.0608

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0327

Gnomad4 FIN

AF:

0.0533

Gnomad4 NFE

AF:

0.0415

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0378

Hom.:

Bravo

AF:

0.0261

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0405

EpiControl

AF:

0.0418

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 06, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Arg193Arg in exon 7 of RSPH1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 4.4% (376/8600) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs149478284). -

Primary ciliary dyskinesia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.59

CADD

Benign

7.0

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over