Genetic Variant RPH3AL:p.Pro292Leu (chr17-215655-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_006987.4(RPH3AL):c.875C>T(p.Pro292Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000892 in 1,278,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

RPH3AL
NM_006987.4 missense, splice_region

Scores

Splicing: ADA: 0.0002630

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.24

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057888925).

BP6

Variant 17-215655-G-A is Benign according to our data. Variant chr17-215655-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3156012.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006987.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPH3AL	NM_006987.4	MANE Select	c.875C>T	p.Pro292Leu	missense splice_region	Exon 9 of 10	NP_008918.1	Q9UNE2-1
RPH3AL	NM_001190411.2		c.875C>T	p.Pro292Leu	missense splice_region	Exon 8 of 9	NP_001177340.1	Q9UNE2-1
RPH3AL	NM_001190412.2		c.788C>T	p.Pro263Leu	missense splice_region	Exon 8 of 9	NP_001177341.1	Q9UNE2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPH3AL	ENST00000331302.12	TSL:2 MANE Select	c.875C>T	p.Pro292Leu	missense splice_region	Exon 9 of 10	ENSP00000328977.7	Q9UNE2-1
RPH3AL	ENST00000323434.12	TSL:1	c.788C>T	p.Pro263Leu	missense splice_region	Exon 8 of 9	ENSP00000319210.8	Q9UNE2-2
RPH3AL	ENST00000953554.1		c.893C>T	p.Pro298Leu	missense splice_region	Exon 8 of 9	ENSP00000623613.1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000313

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000916

AC:

AN:

21842

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000646

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000781

AC:

AN:

1126160

Hom.:

Cov.:

AF XY:

0.0000843

AC XY:

AN XY:

533944

show subpopulations

African (AFR)

AF:

0.000389

AC:

AN:

23122

American (AMR)

AF:

0.000109

AC:

AN:

9178

Ashkenazi Jewish (ASJ)

AF:

0.0000666

AC:

AN:

15012

East Asian (EAS)

AF:

0.000713

AC:

AN:

26652

South Asian (SAS)

AF:

0.000347

AC:

AN:

25936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37846

Middle Eastern (MID)

AF:

0.000659

AC:

AN:

3036

European-Non Finnish (NFE)

AF:

0.0000436

AC:

AN:

939858

Other (OTH)

AF:

0.000132

AC:

AN:

45520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000171

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41594

American (AMR)

AF:

0.000196

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5174

South Asian (SAS)

AF:

0.000621

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000131

AC:

ExAC

AF:

0.0000341

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.7

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.11

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.40

M_CAP

Benign

0.0020

MetaRNN

Benign

0.0058

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

-2.2

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.96

REVEL

Benign

0.0020

Sift

Benign

0.29

Sift4G

Uncertain

0.046

Polyphen

0.0020

Vest4

0.058

MVP

0.24

MPC

0.060

ClinPred

0.055

GERP RS

-6.3

Varity_R

0.034

gMVP

0.12

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00026

dbscSNV1_RF

Benign

0.070

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over