Variant 12-112868593-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001143854.2(RPH3A):c.608G>A(p.Arg203Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,613,614 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 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 Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 112 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 75 hom. )

Consequence

RPH3A
NM_001143854.2 missense, splice_region

Scores

Splicing: ADA: 0.001801

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.41

Variant links:

Genes affected

RPH3A (HGNC:17056): (rabphilin 3A) The protein encoded by this gene is thought to be an effector for RAB3A, which is a small G protein that acts in the late stages of neurotransmitter exocytosis. The encoded protein may be involved in neurotransmitter release and synaptic vesicle traffic. [provided by RefSeq, Dec 2016]

RPH3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022657514).

BP6

Variant 12-112868593-G-A is Benign according to our data. Variant chr12-112868593-G-A is described in ClinVar as [Benign]. Clinvar id is 787101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPH3A	NM_001143854.2 linkuse as main transcript	c.608G>A	p.Arg203Gln	missense_variant, splice_region_variant	8/22	ENST00000389385.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPH3A	ENST00000389385.9 linkuse as main transcript	c.608G>A	p.Arg203Gln	missense_variant, splice_region_variant	8/22	1	NM_001143854.2	P3	Q9Y2J0-1

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2876

AN:

152154

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0648

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00518

AC:

1295

AN:

249942

Hom.:

AF XY:

0.00381

AC XY:

515

AN XY:

135178

show subpopulations

Gnomad AFR exome

AF:

0.0660

Gnomad AMR exome

AF:

0.00464

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0000983

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000505

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00212

AC:

3105

AN:

1461342

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

1357

AN XY:

726916

show subpopulations

Gnomad4 AFR exome

AF:

0.0650

Gnomad4 AMR exome

AF:

0.00528

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000280

Gnomad4 OTH exome

AF:

0.00537

GnomAD4 genome

AF:

0.0189

AC:

2883

AN:

152272

Hom.:

112

Cov.:

AF XY:

0.0181

AC XY:

1348

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0648

Gnomad4 AMR

AF:

0.00915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00346

Hom.:

Bravo

AF:

0.0216

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0651

AC:

287

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00627

AC:

761

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;T;.;T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.051

LIST_S2

Uncertain

0.87

D;.;D;.;D

MetaRNN

Benign

0.0023

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;.;L;.

MutationTaster

Benign

0.62

D;D;D;N;N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.95

N;N;N;N;N

REVEL

Benign

0.056

Sift

Benign

0.20

T;T;T;T;T

Sift4G

Uncertain

0.046

D;D;D;D;T

Polyphen

0.0040

B;B;B;B;B

Vest4

0.10

MVP

0.53

MPC

0.32

ClinPred

0.012

GERP RS

3.2

Varity_R

0.060

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0018

dbscSNV1_RF

Benign

0.042

SpliceAI score (max)

0.0

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