Variant chr12-112847740-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001143854.2(RPH3A):c.128G>A(p.Arg43Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

RPH3A
NM_001143854.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.68

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:

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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=0.19023132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPH3A	NM_001143854.2 link	c.128G>A	p.Arg43Lys	missense_variant	5/22	ENST00000389385.9	NP_001137326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPH3A	ENST00000389385.9 link	c.128G>A	p.Arg43Lys	missense_variant	5/22	1	NM_001143854.2	ENSP00000374036.4		Q9Y2J0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727234

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2024

The c.128G>A (p.R43K) alteration is located in exon 5 (coding exon 3) of the RPH3A gene. This alteration results from a G to A substitution at nucleotide position 128, causing the arginine (R) at amino acid position 43 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0047

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

Eigen

Benign

0.053

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.76

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

M_CAP

Benign

0.019

MetaRNN

Benign

0.19

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

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.68

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

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.56

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.059

Sift

Benign

0.70

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

Sift4G

Benign

1.0

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

Polyphen

0.16, 0.14

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

Vest4

0.42, 0.41, 0.42, 0.41

MutPred

0.35

Gain of ubiquitination at R43 (P = 0.0029);Gain of ubiquitination at R43 (P = 0.0029);Gain of ubiquitination at R43 (P = 0.0029);Gain of ubiquitination at R43 (P = 0.0029);Gain of ubiquitination at R43 (P = 0.0029);Gain of ubiquitination at R43 (P = 0.0029);Gain of ubiquitination at R43 (P = 0.0029);Gain of ubiquitination at R43 (P = 0.0029);Gain of ubiquitination at R43 (P = 0.0029);Gain of ubiquitination at R43 (P = 0.0029);Gain of ubiquitination at R43 (P = 0.0029);Gain of ubiquitination at R43 (P = 0.0029);.;Gain of ubiquitination at R43 (P = 0.0029);Gain of ubiquitination at R43 (P = 0.0029);

MVP

0.49

MPC

0.50

ClinPred

0.83

GERP RS

5.1

Varity_R

0.11

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over