17-215675-G-A

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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0670
Variant links:
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
RPH3ALNM_006987.4 linkc.855C>T p.Pro285Pro synonymous_variant Exon 9 of 10 ENST00000331302.12 NP_008918.1 Q9UNE2-1
RPH3ALNM_001190411.2 linkc.855C>T p.Pro285Pro synonymous_variant Exon 8 of 9 NP_001177340.1 Q9UNE2-1
RPH3ALNM_001190412.2 linkc.768C>T p.Pro256Pro synonymous_variant Exon 8 of 9 NP_001177341.1 Q9UNE2-2A8K7D5
RPH3ALNM_001190413.2 linkc.768C>T p.Pro256Pro synonymous_variant Exon 7 of 8 NP_001177342.1 Q9UNE2-2A8K7D5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPH3ALENST00000331302.12 linkc.855C>T p.Pro285Pro synonymous_variant Exon 9 of 10 2 NM_006987.4 ENSP00000328977.7 Q9UNE2-1

Frequencies

GnomAD3 genomes
AF:
0.00208
AC:
317
AN:
152238
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00658
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.000478
GnomAD2 exomes
AF:
0.000618
AC:
13
AN:
21040
AF XY:
0.000206
show subpopulations
Gnomad AFR exome
AF:
0.00926
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000112
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000240
AC:
270
AN:
1124230
Hom.:
1
Cov.:
31
AF XY:
0.000242
AC XY:
129
AN XY:
533138
show subpopulations
Gnomad4 AFR exome
AF:
0.00424
AC:
98
AN:
23096
Gnomad4 AMR exome
AF:
0.000888
AC:
8
AN:
9014
Gnomad4 ASJ exome
AF:
0.00
AC:
0
AN:
14950
Gnomad4 EAS exome
AF:
0.000150
AC:
4
AN:
26638
Gnomad4 SAS exome
AF:
0.0000771
AC:
2
AN:
25930
Gnomad4 FIN exome
AF:
0.00
AC:
0
AN:
37870
Gnomad4 NFE exome
AF:
0.000142
AC:
133
AN:
938294
Gnomad4 Remaining exome
AF:
0.000463
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:
324
AN:
152356
Hom.:
0
Cov.:
34
AF XY:
0.00201
AC XY:
150
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.00673
AC:
0.00673174
AN:
0.00673174
Gnomad4 AMR
AF:
0.00163
AC:
0.00163313
AN:
0.00163313
Gnomad4 ASJ
AF:
0.00
AC:
0
AN:
0
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 FIN
AF:
0.00
AC:
0
AN:
0
Gnomad4 NFE
AF:
0.000250
AC:
0.000249882
AN:
0.000249882
Gnomad4 OTH
AF:
0.000473
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:
0.000425
Hom.:
0
Bravo
AF:
0.00227
Asia WGS
AF:
0.000289
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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
8.2
DANN
Benign
0.69
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs182695940; hg19: chr17-65466; API