21-42475879-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_080860.4(RSPH1):​c.877+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,608,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 27)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

RSPH1
NM_080860.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.633
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 21-42475879-C-T is Benign according to our data. Variant chr21-42475879-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3691068.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RSPH1NM_080860.4 linkc.877+19G>A intron_variant Intron 8 of 8 ENST00000291536.8 NP_543136.1 Q8WYR4-1
RSPH1NM_001286506.2 linkc.763+19G>A intron_variant Intron 7 of 7 NP_001273435.1 Q8WYR4-2
RSPH1XM_011529786.2 linkc.805+19G>A intron_variant Intron 7 of 7 XP_011528088.1
RSPH1XM_005261208.3 linkc.670+19G>A intron_variant Intron 6 of 6 XP_005261265.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RSPH1ENST00000291536.8 linkc.877+19G>A intron_variant Intron 8 of 8 1 NM_080860.4 ENSP00000291536.3 Q8WYR4-1
RSPH1ENST00000398352.3 linkc.763+19G>A intron_variant Intron 7 of 7 5 ENSP00000381395.3 Q8WYR4-2
RSPH1ENST00000493019.1 linkn.2495+19G>A intron_variant Intron 7 of 7 2

Frequencies

GnomAD3 genomes
AF:
0.0000204
AC:
3
AN:
147218
Hom.:
0
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000447
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461516
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727092
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000204
AC:
3
AN:
147218
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
71336
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000447
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Benign:1
Mar 07, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.27
DANN
Benign
0.37

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

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

Other links and lift over

dbSNP: rs1424381489; hg19: chr21-43895989; API