Variant 7-6763957-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001099697.2(RSPH10B2):c.429C>A(p.Asn143Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000074 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RSPH10B2
NM_001099697.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.403

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21861237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH10B2	NM_001099697.2 linkuse as main transcript	c.429C>A	p.Asn143Lys	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.429C>A	p.Asn143Lys	missense_variant	6/21	1	NM_001099697.2	ENSP00000386102	P1	B2RC85-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148020

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000749

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000133

AC:

AN:

224842

Hom.:

AF XY:

0.00000819

AC XY:

AN XY:

122046

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000632

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:

0.00

Gnomad OTH exome

AF:

0.000181

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000424

AC:

AN:

1415822

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

705920

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000140

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000743

AC:

AN:

148020

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

72112

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000749

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Nov 21, 2023

The c.429C>A (p.N143K) alteration is located in exon 6 (coding exon 4) of the RSPH10B2 gene. This alteration results from a C to A substitution at nucleotide position 429, causing the asparagine (N) at amino acid position 143 to be replaced by a lysine (K). 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

0.40

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.087

T;T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.79

.;.;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.14

N;N;N

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Uncertain

0.30

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.97

D;D;D

Vest4

0.30

MutPred

0.73

Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);

MVP

0.12

ClinPred

0.35

GERP RS

0.18

Varity_R

0.21

gMVP

0.58

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