Variant 7-5926496-C-T 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_173565.5(RSPH10B):c.2485G>A(p.Val829Met) 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 0.00017 ( 0 hom., cov: 20)

Exomes 𝑓: 0.00038 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

RSPH10B
NM_173565.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.94

Variant links:

Genes affected

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

RSPH10B links:

CCZ1 (HGNC:21691): (CCZ1 homolog, vacuolar protein trafficking and biogenesis associated) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in vesicle-mediated transport. Located in intracellular membrane-bounded organelle. Part of Mon1-Ccz1 complex. [provided by Alliance of Genome Resources, Apr 2022]

CCZ1 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=0.024126649).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH10B	NM_173565.5 linkuse as main transcript	c.2485G>A	p.Val829Met	missense_variant	21/21	ENST00000404406.6	NP_775836.4
CCZ1	NM_015622.6 linkuse as main transcript	c.*809C>T		3_prime_UTR_variant	15/15	ENST00000325974.9	NP_056437.4	P86790P86791

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH10B	ENST00000404406.6 linkuse as main transcript	c.2485G>A	p.Val829Met	missense_variant	21/21	1	NM_173565.5	ENSP00000384097.1		P0C881
CCZ1	ENST00000325974.9 linkuse as main transcript	c.*809C>T		3_prime_UTR_variant	15/15	1	NM_015622.6	ENSP00000325681.6		P86791

Frequencies

GnomAD3 genomes

AF:

0.000167

AC:

AN:

149378

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000734

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000676

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:

0.000299

Gnomad OTH

AF:

0.000493

GnomAD3 exomes

AF:

0.000133

AC:

AN:

247614

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

134056

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000272

Gnomad OTH exome

AF:

0.000493

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000377

AC:

549

AN:

1454906

Hom.:

Cov.:

AF XY:

0.000387

AC XY:

280

AN XY:

723892

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000473

Gnomad4 OTH exome

AF:

0.000366

GnomAD4 genome

AF:

0.000167

AC:

AN:

149496

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

73052

show subpopulations

Gnomad4 AFR

AF:

0.0000732

Gnomad4 AMR

AF:

0.0000675

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000299

Gnomad4 OTH

AF:

0.000487

Alfa

AF:

0.000158

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000467

AC:

ExAC

AF:

0.000140

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

Aug 17, 2022

The c.2485G>A (p.V829M) alteration is located in exon 21 (coding exon 19) of the RSPH10B gene. This alteration results from a G to A substitution at nucleotide position 2485, causing the valine (V) at amino acid position 829 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

0.13

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.063

DANN

Benign

0.85

DEOGEN2

Benign

0.0080

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.61

T;.;.

M_CAP

Benign

0.016

MetaRNN

Benign

0.024

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

L;L;L

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.45

N;N;N

REVEL

Benign

0.037

Sift

Uncertain

0.012

D;D;D

Sift4G

Uncertain

0.057

T;T;T

Polyphen

0.0090

B;B;B

Vest4

0.14

MVP

0.088

ClinPred

0.043

GERP RS

-5.9

Varity_R

0.034

gMVP

0.050

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