Variant 7-6763964-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001099697.2(RSPH10B2):c.436G>A(p.Val146Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000058 ( 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: -0.629

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.050237477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH10B2	NM_001099697.2 linkuse as main transcript	c.436G>A	p.Val146Met	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.436G>A	p.Val146Met	missense_variant	6/21	1	NM_001099697.2	ENSP00000386102	P1	B2RC85-1

Frequencies

GnomAD3 genomes

AF:

0.000129

AC:

AN:

147468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000684

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000597

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000909

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

201176

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

109342

show subpopulations

Gnomad AFR exome

AF:

0.0000736

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000555

Gnomad SAS exome

AF:

0.0000398

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000911

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000579

AC:

AN:

1398868

Hom.:

Cov.:

AF XY:

0.0000587

AC XY:

AN XY:

698208

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.0000461

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000482

Gnomad4 SAS exome

AF:

0.0000472

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000464

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000129

AC:

AN:

147570

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

71906

show subpopulations

Gnomad4 AFR

AF:

0.000222

Gnomad4 AMR

AF:

0.0000683

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000598

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000909

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000960

Hom.:

ExAC

AF:

0.0000663

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

Nov 21, 2023

The c.436G>A (p.V146M) 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 436, causing the valine (V) at amino acid position 146 to be replaced by a methionine (M). 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

0.071

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.27

DANN

Benign

0.96

DEOGEN2

Benign

0.0074

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0082

LIST_S2

Benign

0.67

.;.;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.050

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.94

L;L;L

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.76

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.24

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.54

P;P;P

Vest4

0.17

MutPred

0.56

Gain of disorder (P = 0.0852);Gain of disorder (P = 0.0852);Gain of disorder (P = 0.0852);

MVP

0.040

ClinPred

0.020

GERP RS

-4.1

Varity_R

0.038

gMVP

0.20

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