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GeneBe

17-215675-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_006987.4(RPH3AL):c.855C>T(p.Pro285=) 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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
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/exons MANE UniProt
RPH3ALNM_006987.4 linkuse as main transcriptc.855C>T p.Pro285= synonymous_variant 9/10 ENST00000331302.12
RPH3ALNM_001190411.2 linkuse as main transcriptc.855C>T p.Pro285= synonymous_variant 8/9
RPH3ALNM_001190412.2 linkuse as main transcriptc.768C>T p.Pro256= synonymous_variant 8/9
RPH3ALNM_001190413.2 linkuse as main transcriptc.768C>T p.Pro256= synonymous_variant 7/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPH3ALENST00000331302.12 linkuse as main transcriptc.855C>T p.Pro285= synonymous_variant 9/102 NM_006987.4 P1Q9UNE2-1

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
GnomAD3 exomes
AF:
0.000618
AC:
13
AN:
21040
Hom.:
0
AF XY:
0.000206
AC XY:
2
AN XY:
9714
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 SAS 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
Gnomad4 AMR exome
AF:
0.000888
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000150
Gnomad4 SAS exome
AF:
0.0000771
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000142
Gnomad4 OTH exome
AF:
0.000463
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
Gnomad4 AMR
AF:
0.00163
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.000473
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
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2023RPH3AL: 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

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