chr7-5926499-C-T

Variant summary

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

The ENST00000404406.6(RSPH10B):​c.2482G>A​(p.Glu828Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 21)
Exomes 𝑓: 0.000092 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RSPH10B
ENST00000404406.6 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22
Variant links:
Genes affected
RSPH10B (HGNC:27362): (radial spoke head 10 homolog B)
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]

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=0.04382798).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RSPH10BNM_173565.5 linkuse as main transcriptc.2482G>A p.Glu828Lys missense_variant 21/21 ENST00000404406.6 NP_775836.4
CCZ1NM_015622.6 linkuse as main transcriptc.*812C>T 3_prime_UTR_variant 15/15 ENST00000325974.9 NP_056437.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RSPH10BENST00000404406.6 linkuse as main transcriptc.2482G>A p.Glu828Lys missense_variant 21/211 NM_173565.5 ENSP00000384097 P1
CCZ1ENST00000325974.9 linkuse as main transcriptc.*812C>T 3_prime_UTR_variant 15/151 NM_015622.6 ENSP00000325681 P1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
8
AN:
149478
Hom.:
0
Cov.:
21
FAILED QC
Gnomad AFR
AF:
0.0000733
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:
0.0000748
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000969
AC:
24
AN:
247638
Hom.:
0
AF XY:
0.0000970
AC XY:
13
AN XY:
134070
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.0000291
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:
0.000199
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000921
AC:
134
AN:
1455050
Hom.:
0
Cov.:
31
AF XY:
0.0000884
AC XY:
64
AN XY:
723950
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000112
Gnomad4 OTH exome
AF:
0.0000832
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000535
AC:
8
AN:
149596
Hom.:
0
Cov.:
21
AF XY:
0.0000274
AC XY:
2
AN XY:
73076
show subpopulations
Gnomad4 AFR
AF:
0.0000731
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:
0.0000748
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000961
Hom.:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000117
AC:
1
ExAC
AF:
0.000157
AC:
19

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 submitterclinical testingAmbry GeneticsJul 14, 2022The c.2482G>A (p.E828K) 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 2482, causing the glutamic acid (E) at amino acid position 828 to be replaced by a lysine (K). 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
0.11
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.021
T;T;T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.048
N
LIST_S2
Benign
0.79
T;.;.
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.044
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.7
L;L;L
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Benign
0.073
Sift
Uncertain
0.022
D;D;D
Sift4G
Uncertain
0.031
D;D;D
Polyphen
0.42
B;B;B
Vest4
0.28
MVP
0.16
ClinPred
0.027
T
GERP RS
2.5
Varity_R
0.14
gMVP
0.096

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.

Other links and lift over

dbSNP: rs202032733; hg19: chr7-5966130; API