Variant chr7-6779690-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000404077.6(RSPH10B2):c.1495C>T(p.His499Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 147 hom., cov: 12)

Exomes 𝑓: 0.019 ( 765 hom. )

Consequence

RSPH10B2
ENST00000404077.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.951

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003009528).

BP6

Variant 7-6779690-C-T is Benign according to our data. Variant chr7-6779690-C-T is described in ClinVar as [Benign]. Clinvar id is 770736.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0163 (1571/96094) while in subpopulation NFE AF= 0.0254 (1211/47606). AF 95% confidence interval is 0.0242. There are 147 homozygotes in gnomad4. There are 664 alleles in male gnomad4 subpopulation. Median coverage is 12. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 147 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH10B2	NM_001099697.2 linkuse as main transcript	c.1495C>T	p.His499Tyr	missense_variant	13/21	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.1495C>T	p.His499Tyr	missense_variant	13/21	1	NM_001099697.2	ENSP00000386102.1		B2RC85-1

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

1574

AN:

96016

Hom.:

148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00546

Gnomad AMI

AF:

0.00977

Gnomad AMR

AF:

0.0131

Gnomad ASJ

AF:

0.0227

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00535

Gnomad FIN

AF:

0.00460

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0255

Gnomad OTH

AF:

0.0157

GnomAD3 exomes

AF:

0.0142

AC:

585

AN:

41294

Hom.:

AF XY:

0.0140

AC XY:

290

AN XY:

20680

show subpopulations

Gnomad AFR exome

AF:

0.00375

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00386

Gnomad FIN exome

AF:

0.00518

Gnomad NFE exome

AF:

0.0258

Gnomad OTH exome

AF:

0.00843

GnomAD4 exome

AF:

0.0193

AC:

6162

AN:

319248

Hom.:

765

Cov.:

AF XY:

0.0188

AC XY:

3149

AN XY:

167586

show subpopulations

Gnomad4 AFR exome

AF:

0.00536

Gnomad4 AMR exome

AF:

0.0102

Gnomad4 ASJ exome

AF:

0.0205

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00550

Gnomad4 FIN exome

AF:

0.00674

Gnomad4 NFE exome

AF:

0.0265

Gnomad4 OTH exome

AF:

0.0171

GnomAD4 genome

AF:

0.0163

AC:

1571

AN:

96094

Hom.:

147

Cov.:

AF XY:

0.0148

AC XY:

664

AN XY:

45010

show subpopulations

Gnomad4 AFR

AF:

0.00544

Gnomad4 AMR

AF:

0.0129

Gnomad4 ASJ

AF:

0.0227

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00535

Gnomad4 FIN

AF:

0.00460

Gnomad4 NFE

AF:

0.0254

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0178

Hom.:

ExAC

AF:

0.0116

AC:

884

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.30

DEOGEN2

Benign

0.0058

T;T;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.48

.;.;T

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.20

N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0080

B;B;B

Vest4

0.069

ClinPred

0.0059

GERP RS

3.6

Varity_R

0.063

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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