Variant 21-42475919-ACTC-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting

The NM_080860.4(RSPH1):c.853_855del(p.Glu285del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,607,900 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000068 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

RSPH1
NM_080860.4 inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.915

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_080860.4. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RSPH1	NM_080860.4 linkuse as main transcript	c.853_855del	p.Glu285del	inframe_deletion	8/9	ENST00000291536.8
RSPH1	NM_001286506.2 linkuse as main transcript	c.739_741del	p.Glu247del	inframe_deletion	7/8
RSPH1	XM_005261208.3 linkuse as main transcript	c.646_648del	p.Glu216del	inframe_deletion	6/7
RSPH1	XM_011529786.2 linkuse as main transcript	c.781_783del	p.Glu261del	inframe_deletion	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPH1	ENST00000291536.8 linkuse as main transcript	c.853_855del	p.Glu285del	inframe_deletion	8/9	1	NM_080860.4	P1	Q8WYR4-1
RSPH1	ENST00000398352.3 linkuse as main transcript	c.739_741del	p.Glu247del	inframe_deletion	7/8	5			Q8WYR4-2
RSPH1	ENST00000493019.1 linkuse as main transcript	n.2471_2473del		non_coding_transcript_exon_variant	7/8	2

Frequencies

GnomAD3 genomes

AF:

0.0000685

AC:

AN:

145944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000509

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000693

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:

0.000105

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000111

AC:

AN:

251428

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000233

AC:

341

AN:

1461836

Hom.:

AF XY:

0.000237

AC XY:

172

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

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:

0.000297

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000685

AC:

AN:

146064

Hom.:

Cov.:

AF XY:

0.0000988

AC XY:

AN XY:

70832

show subpopulations

Gnomad4 AFR

AF:

0.0000507

Gnomad4 AMR

AF:

0.0000692

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000105

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000226

Hom.:

Bravo

AF:

0.0000793

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Aug 09, 2022

This variant, c.853_855del, results in the deletion of 1 amino acid(s) of the RSPH1 protein (p.Glu285del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs562822292, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RSPH1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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