Variant rs139625725 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_080860.4(RSPH1):c.546A>G(p.Gln182Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000679 in 1,613,510 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 5 hom. )

Consequence

RSPH1
NM_080860.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.637

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:

RSPH1 (HGNC:):

RSPH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 21-42482664-T-C is Benign according to our data. Variant chr21-42482664-T-C is described in ClinVar as [Benign]. Clinvar id is 414805.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.637 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000702 (1026/1461158) while in subpopulation SAS AF= 0.00483 (416/86114). AF 95% confidence interval is 0.00445. There are 5 homozygotes in gnomad4_exome. There are 637 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH1	NM_080860.4 linkuse as main transcript	c.546A>G	p.Gln182Gln	synonymous_variant	6/9	ENST00000291536.8	NP_543136.1	Q8WYR4-1
RSPH1	NM_001286506.2 linkuse as main transcript	c.432A>G	p.Gln144Gln	synonymous_variant	5/8		NP_001273435.1	Q8WYR4-2
RSPH1	XM_005261208.3 linkuse as main transcript	c.339A>G	p.Gln113Gln	synonymous_variant	4/7		XP_005261265.1
RSPH1	XM_011529786.2 linkuse as main transcript	c.501+3005A>G		intron_variant			XP_011528088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RSPH1	ENST00000291536.8 linkuse as main transcript	c.546A>G	p.Gln182Gln	synonymous_variant	6/9	1	NM_080860.4	ENSP00000291536.3	Q8WYR4-1
RSPH1	ENST00000398352.3 linkuse as main transcript	c.432A>G	p.Gln144Gln	synonymous_variant	5/8	5		ENSP00000381395.3	Q8WYR4-2
RSPH1	ENST00000493019.1 linkuse as main transcript	n.2164A>G		non_coding_transcript_exon_variant	5/8	2

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00106

AC:

267

AN:

250936

Hom.:

AF XY:

0.00133

AC XY:

180

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000670

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00443

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000616

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000702

AC:

1026

AN:

1461158

Hom.:

Cov.:

AF XY:

0.000876

AC XY:

637

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000674

Gnomad4 ASJ exome

AF:

0.00364

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00483

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000360

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.000453

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000762

Hom.:

Bravo

AF:

0.000468

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.1

DANN

Benign

0.44

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.

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