Variant 7-5943358-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173565.5(RSPH10B):c.1724C>T(p.Thr575Met) variant causes a missense change. The variant allele was found at a frequency of 0.00014 in 1,590,458 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

RSPH10B
NM_173565.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09

Variant links:

Genes affected

RSPH10B (HGNC:27362): (radial spoke head 10 homolog B)

RSPH10B links:

RSPH10B (HGNC:):

RSPH10B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH10B	NM_173565.5 linkuse as main transcript	c.1724C>T	p.Thr575Met	missense_variant	15/21	ENST00000404406.6	NP_775836.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH10B	ENST00000404406.6 linkuse as main transcript	c.1724C>T	p.Thr575Met	missense_variant	15/21	1	NM_173565.5	ENSP00000384097.1		P0C881

Frequencies

GnomAD3 genomes

AF:

0.000153

AC:

AN:

150120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000192

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

234540

Hom.:

AF XY:

0.0000704

AC XY:

AN XY:

127844

show subpopulations

Gnomad AFR exome

AF:

0.000202

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000345

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000951

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000137

AC:

197

AN:

1440218

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

714548

show subpopulations

Gnomad4 AFR exome

AF:

0.000743

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000136

Gnomad4 OTH exome

AF:

0.000337

GnomAD4 genome

AF:

0.000166

AC:

AN:

150240

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

73396

show subpopulations

Gnomad4 AFR

AF:

0.000271

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000192

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.0000480

Hom.:

ESP6500AA

AF:

0.000231

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000661

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

Jan 20, 2023

The c.1724C>T (p.T575M) alteration is located in exon 15 (coding exon 13) of the RSPH10B gene. This alteration results from a C to T substitution at nucleotide position 1724, causing the threonine (T) at amino acid position 575 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

0.19

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T;T

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.84

T;.;.

M_CAP

Benign

0.073

MetaRNN

Uncertain

0.54

D;D;D

MetaSVM

Uncertain

-0.24

MutationAssessor

Uncertain

2.2

M;M;M

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.57

MVP

0.46

ClinPred

0.34

GERP RS

3.4

Varity_R

0.12

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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