7-6781355-C-T

Position:

chr7-6781355-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001099697.2(RSPH10B2):c.1637C>T(p.Thr546Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,259,192 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00035 ( 13 hom., cov: 17)

Exomes 𝑓: 0.00050 ( 141 hom. )

Consequence

RSPH10B2
NM_001099697.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 2.11

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 Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11353114).

BP6

Variant 7-6781355-C-T is Benign according to our data. Variant chr7-6781355-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2350217.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH10B2	NM_001099697.2 linkuse as main transcript	c.1637C>T	p.Thr546Met	missense_variant	15/21	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.1637C>T	p.Thr546Met	missense_variant	15/21	1	NM_001099697.2	ENSP00000386102	P1	B2RC85-1

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

115036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000101

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000794

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000498

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000358

AC:

AN:

156214

Hom.:

AF XY:

0.000358

AC XY:

AN XY:

83798

show subpopulations

Gnomad AFR exome

AF:

0.000277

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000197

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000263

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000589

Gnomad OTH exome

AF:

0.000742

GnomAD4 exome

AF:

0.000497

AC:

569

AN:

1144156

Hom.:

141

Cov.:

AF XY:

0.000509

AC XY:

287

AN XY:

564194

show subpopulations

Gnomad4 AFR exome

AF:

0.000122

Gnomad4 AMR exome

AF:

0.0000785

Gnomad4 ASJ exome

AF:

0.000433

Gnomad4 EAS exome

AF:

0.000192

Gnomad4 SAS exome

AF:

0.000367

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000552

Gnomad4 OTH exome

AF:

0.000700

GnomAD4 genome

AF:

0.000348

AC:

AN:

115036

Hom.:

Cov.:

AF XY:

0.000308

AC XY:

AN XY:

55144

show subpopulations

Gnomad4 AFR

AF:

0.000306

Gnomad4 AMR

AF:

0.000101

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000794

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000498

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

ESP6500AA

AF:

0.000299

AC:

ESP6500EA

AF:

0.00109

AC:

ExAC

AF:

0.000417

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.1637C>T (p.T546M) alteration is located in exon 15 (coding exon 13) of the RSPH10B2 gene. This alteration results from a C to T substitution at nucleotide position 1637, causing the threonine (T) at amino acid position 546 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

RSPH10B2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

T;T;T

Eigen

Benign

-0.092

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.81

.;.;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.1

M;M;M

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.024

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.52

MVP

0.11

ClinPred

0.088

GERP RS

3.4

Varity_R

0.11

gMVP

0.43

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