dbSNP rs568520768: RPH3AL:p.Arg171Leu (chr17-247212-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006987.4(RPH3AL):c.512G>T(p.Arg171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

RPH3AL
NM_006987.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00800

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11144632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPH3AL	NM_006987.4 link	c.512G>T	p.Arg171Leu	missense_variant	Exon 7 of 10	ENST00000331302.12	NP_008918.1	Q9UNE2-1
RPH3AL	NM_001190411.2 link	c.512G>T	p.Arg171Leu	missense_variant	Exon 6 of 9		NP_001177340.1	Q9UNE2-1
RPH3AL	NM_001190412.2 link	c.425G>T	p.Arg142Leu	missense_variant	Exon 6 of 9		NP_001177341.1	Q9UNE2-2A8K7D5
RPH3AL	NM_001190413.2 link	c.425G>T	p.Arg142Leu	missense_variant	Exon 5 of 8		NP_001177342.1	Q9UNE2-2A8K7D5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3AL	ENST00000331302.12 link	c.512G>T	p.Arg171Leu	missense_variant	Exon 7 of 10	2	NM_006987.4	ENSP00000328977.7		Q9UNE2-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250926

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461434

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;T;.;.;T;T;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.80

T;.;.;T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.11

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;.;.;.;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.9

.;.;.;N;.;.;.

REVEL

Benign

0.045

Sift

Uncertain

0.023

.;.;.;D;.;.;.

Sift4G

Benign

0.081

T;T;T;T;.;.;.

Polyphen

0.031

B;B;B;B;.;.;.

Vest4

0.36

MutPred

0.59

Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);.;.;Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);.;

MVP

0.46

MPC

0.12

ClinPred

0.049

GERP RS

0.49

Varity_R

0.095

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over