17-215675-G-A
Variant names:
Variant summary
Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_006987.4(RPH3AL):c.855C>T(p.Pro285Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000465 in 1,276,586 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0021 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00024 ( 1 hom. )
Consequence
RPH3AL
NM_006987.4 synonymous
NM_006987.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0670
Genes affected
RPH3AL (HGNC:10296): (rabphilin 3A like (without C2 domains)) The protein encoded by this gene plays a direct regulatory role in calcium-ion-dependent exocytosis in both endocrine and exocrine cells and plays a key role in insulin secretion by pancreatic cells. This gene is likely a tumor suppressor. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jun 2010]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -7 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 17-215675-G-A is Benign according to our data. Variant chr17-215675-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647153.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.067 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RPH3AL | NM_006987.4 | c.855C>T | p.Pro285Pro | synonymous_variant | Exon 9 of 10 | ENST00000331302.12 | NP_008918.1 | |
RPH3AL | NM_001190411.2 | c.855C>T | p.Pro285Pro | synonymous_variant | Exon 8 of 9 | NP_001177340.1 | ||
RPH3AL | NM_001190412.2 | c.768C>T | p.Pro256Pro | synonymous_variant | Exon 8 of 9 | NP_001177341.1 | ||
RPH3AL | NM_001190413.2 | c.768C>T | p.Pro256Pro | synonymous_variant | Exon 7 of 8 | NP_001177342.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00208 AC: 317AN: 152238Hom.: 0 Cov.: 34 show subpopulations
GnomAD3 genomes
AF:
AC:
317
AN:
152238
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.000618 AC: 13AN: 21040 AF XY: 0.000206 show subpopulations
GnomAD2 exomes
AF:
AC:
13
AN:
21040
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000240 AC: 270AN: 1124230Hom.: 1 Cov.: 31 AF XY: 0.000242 AC XY: 129AN XY: 533138 show subpopulations
GnomAD4 exome
AF:
AC:
270
AN:
1124230
Hom.:
Cov.:
31
AF XY:
AC XY:
129
AN XY:
533138
Gnomad4 AFR exome
AF:
AC:
98
AN:
23096
Gnomad4 AMR exome
AF:
AC:
8
AN:
9014
Gnomad4 ASJ exome
AF:
AC:
0
AN:
14950
Gnomad4 EAS exome
AF:
AC:
4
AN:
26638
Gnomad4 SAS exome
AF:
AC:
2
AN:
25930
Gnomad4 FIN exome
AF:
AC:
0
AN:
37870
Gnomad4 NFE exome
AF:
AC:
133
AN:
938294
Gnomad4 Remaining exome
AF:
AC:
21
AN:
45392
Heterozygous variant carriers
0
18
35
53
70
88
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.00213 AC: 324AN: 152356Hom.: 0 Cov.: 34 AF XY: 0.00201 AC XY: 150AN XY: 74500 show subpopulations
GnomAD4 genome
AF:
AC:
324
AN:
152356
Hom.:
Cov.:
34
AF XY:
AC XY:
150
AN XY:
74500
Gnomad4 AFR
AF:
AC:
0.00673174
AN:
0.00673174
Gnomad4 AMR
AF:
AC:
0.00163313
AN:
0.00163313
Gnomad4 ASJ
AF:
AC:
0
AN:
0
Gnomad4 EAS
AF:
AC:
0
AN:
0
Gnomad4 SAS
AF:
AC:
0
AN:
0
Gnomad4 FIN
AF:
AC:
0
AN:
0
Gnomad4 NFE
AF:
AC:
0.000249882
AN:
0.000249882
Gnomad4 OTH
AF:
AC:
0.00047259
AN:
0.00047259
Heterozygous variant carriers
0
14
28
41
55
69
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
May 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
RPH3AL: BP4, BP7 -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
Mutation Taster
=100/0
polymorphism
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at