Variant 17-215675-G-A details in Genebe, Genetics Data Aggregator

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

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]

RPH3AL links:

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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	Protein
RPH3AL	NM_006987.4 linkuse as main transcript	c.855C>T	p.Pro285=	synonymous_variant	9/10	ENST00000331302.12	NP_008918.1
RPH3AL	NM_001190411.2 linkuse as main transcript	c.855C>T	p.Pro285=	synonymous_variant	8/9		NP_001177340.1
RPH3AL	NM_001190412.2 linkuse as main transcript	c.768C>T	p.Pro256=	synonymous_variant	8/9		NP_001177341.1
RPH3AL	NM_001190413.2 linkuse as main transcript	c.768C>T	p.Pro256=	synonymous_variant	7/8		NP_001177342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPH3AL	ENST00000331302.12 linkuse as main transcript	c.855C>T	p.Pro285=	synonymous_variant	9/10	2	NM_006987.4	ENSP00000328977	P1	Q9UNE2-1

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

317

AN:

152238

Hom.:

Cov.:

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:

AN:

21040

Hom.:

AF XY:

0.000206

AC XY:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00227

Asia WGS

AF:

0.000289

AC:

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 submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

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

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.

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