rs1057501981

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080860.4(RSPH1):​c.877+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 27)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RSPH1
NM_080860.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.28
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RSPH1NM_080860.4 linkc.877+14G>T intron_variant Intron 8 of 8 ENST00000291536.8 NP_543136.1 Q8WYR4-1
RSPH1NM_001286506.2 linkc.763+14G>T intron_variant Intron 7 of 7 NP_001273435.1 Q8WYR4-2
RSPH1XM_011529786.2 linkc.805+14G>T intron_variant Intron 7 of 7 XP_011528088.1
RSPH1XM_005261208.3 linkc.670+14G>T 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+14G>T intron_variant Intron 8 of 8 1 NM_080860.4 ENSP00000291536.3 Q8WYR4-1
RSPH1ENST00000398352.3 linkc.763+14G>T intron_variant Intron 7 of 7 5 ENSP00000381395.3 Q8WYR4-2
RSPH1ENST00000493019.1 linkn.2495+14G>T intron_variant Intron 7 of 7 2

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461550
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727104
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.14
DANN
Benign
0.42

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: rs1057501981; hg19: chr21-43895994; API