Variant 7-5943434-T-C 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.1648A>G(p.Met550Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000269 in 1,597,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

RSPH10B
NM_173565.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.15

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.1648A>G	p.Met550Val	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.1648A>G	p.Met550Val	missense_variant	15/21	1	NM_173565.5	ENSP00000384097.1		P0C881

Frequencies

GnomAD3 genomes

AF:

0.000159

AC:

AN:

150888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000565

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000670

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000502

AC:

AN:

238858

Hom.:

AF XY:

0.0000231

AC XY:

AN XY:

130080

show subpopulations

Gnomad AFR exome

AF:

0.000730

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1446528

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

720056

show subpopulations

Gnomad4 AFR exome

AF:

0.000521

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000159

AC:

AN:

151006

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

AN XY:

73812

show subpopulations

Gnomad4 AFR

AF:

0.000563

Gnomad4 AMR

AF:

0.0000669

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000213

Hom.:

ESP6500AA

AF:

0.000925

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000743

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 26, 2022

The c.1648A>G (p.M550V) alteration is located in exon 15 (coding exon 13) of the RSPH10B gene. This alteration results from a A to G substitution at nucleotide position 1648, causing the methionine (M) at amino acid position 550 to be replaced by a valine (V). 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

0.089

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.56

DEOGEN2

Benign

0.012

T;T;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.70

T;.;.

M_CAP

Benign

0.037

MetaRNN

Benign

0.033

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.2

M;M;M

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.018

D;D;D

Sift4G

Benign

0.12

T;T;T

Polyphen

0.28

B;B;B

Vest4

0.26

MVP

0.26

ClinPred

0.059

GERP RS

3.4

Varity_R

0.33

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.24

Position offset: 1

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