Variant 7-6764091-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The ENST00000404077.6(RSPH10B2):c.563G>A(p.Arg188Gln) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 18)

Exomes 𝑓: 0.000045 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RSPH10B2
ENST00000404077.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.45

Variant links:

Genes affected

RSPH10B2 (HGNC:34385): (radial spoke head 10 homolog B2) This gene encodes a protein component of the radial spoke head in flagella and motile cilia. Eukaryotic flagella and motile cilia share a common 9 + 2 structure, in which nine peripheral microtubule doublets (MTDs) surround a central-pair of microtubules (CP), with radial spokes connecting the MTDs to the CP. The radial spoke is a multi-protein complex that works as a mechanochemical transducer between the CP and the MTDs. The radial spoke contributes to the regulation of the activity of dynein motors, and thus to flagellar motility. PMID: 22754630 provides a good review of radial spokes. [provided by RefSeq, Jul 2017]

RSPH10B2 links:

RSPH10B2 (HGNC:):

RSPH10B2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2937249).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH10B2	NM_001099697.2 linkuse as main transcript	c.563G>A	p.Arg188Gln	missense_variant	6/21	ENST00000404077.6	NP_001093167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH10B2	ENST00000404077.6 linkuse as main transcript	c.563G>A	p.Arg188Gln	missense_variant	6/21	1	NM_001099697.2	ENSP00000386102.1		B2RC85-1

Frequencies

GnomAD3 genomes

AF:

0.0000803

AC:

AN:

137040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000215

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:

0.0000477

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000112

AC:

AN:

124474

Hom.:

AF XY:

0.0000921

AC XY:

AN XY:

65182

show subpopulations

Gnomad AFR exome

AF:

0.000523

Gnomad AMR exome

AF:

0.0000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000885

Gnomad SAS exome

AF:

0.000172

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000935

Gnomad OTH exome

AF:

0.000279

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000451

AC:

AN:

1151786

Hom.:

Cov.:

AF XY:

0.0000451

AC XY:

AN XY:

576652

show subpopulations

Gnomad4 AFR exome

AF:

0.000343

Gnomad4 AMR exome

AF:

0.0000532

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000550

Gnomad4 SAS exome

AF:

0.000274

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000177

Gnomad4 OTH exome

AF:

0.0000403

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000803

AC:

AN:

137040

Hom.:

Cov.:

AF XY:

0.0000909

AC XY:

AN XY:

65976

show subpopulations

Gnomad4 AFR

AF:

0.000215

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:

0.0000477

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000961

Hom.:

ExAC

AF:

0.0000693

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.563G>A (p.R188Q) alteration is located in exon 6 (coding exon 4) of the RSPH10B2 gene. This alteration results from a G to A substitution at nucleotide position 563, causing the arginine (R) at amino acid position 188 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

T;T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

.;.;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.53

MutationTaster

Benign

0.87

D;D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.2

D;D;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.77

MVP

0.18

ClinPred

0.24

GERP RS

3.4

Varity_R

0.46

gMVP

0.63

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