Variant chr7-6780876-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000404077.6(RSPH10B2):c.1597T>G(p.Cys533Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000668 in 1,498,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000084 ( 0 hom., cov: 18)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

RSPH10B2
ENST00000404077.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16470355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH10B2	NM_001099697.2 linkuse as main transcript	c.1597T>G	p.Cys533Gly	missense_variant	14/21	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.1597T>G	p.Cys533Gly	missense_variant	14/21	1	NM_001099697.2	ENSP00000386102.1		B2RC85-1

Frequencies

GnomAD3 genomes

AF:

0.00000839

AC:

AN:

119254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000262

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:

0.0000380

AC:

AN:

237104

Hom.:

AF XY:

0.0000544

AC XY:

AN XY:

128672

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000541

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000653

AC:

AN:

1378788

Hom.:

Cov.:

AF XY:

0.00000880

AC XY:

AN XY:

681508

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000270

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

AF:

0.00000839

AC:

AN:

119254

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

57484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000262

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000247

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

Oct 04, 2022

The c.1597T>G (p.C533G) alteration is located in exon 14 (coding exon 12) of the RSPH10B2 gene. This alteration results from a T to G substitution at nucleotide position 1597, causing the cysteine (C) at amino acid position 533 to be replaced by a glycine (G). 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

Benign

0.13

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.074

T;T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.60

.;.;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.2

M;M;M

MutationTaster

Benign

0.99

D;N;N;N;N

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-6.7

D;D;D

REVEL

Benign

0.27

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.22

T;T;T

Polyphen

0.26

B;B;B

Vest4

0.50

MutPred

0.62

Loss of stability (P = 0.0132);Loss of stability (P = 0.0132);Loss of stability (P = 0.0132);

MVP

0.48

ClinPred

0.17

GERP RS

3.8

Varity_R

0.37

gMVP

0.26

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