rs10492025

Variant names:

• chr12-112835245-C-T
• rs10492025
• NM_001143854.2:c.72-1246C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143854.2(RPH3A):​c.72-1246C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,034 control chromosomes in the GnomAD database, including 7,752 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7752 hom., cov: 33)
• Consequence: RPH3A NM_001143854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• congenital myasthenic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPH3A	NM_001143854.2	c.72-1246C>T		intron_variant	Intron 3 of 21	ENST00000389385.9	NP_001137326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3A	ENST00000389385.9	c.72-1246C>T		intron_variant	Intron 3 of 21	1	NM_001143854.2	ENSP00000374036.4

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47593 AN: 151916 Hom.: 7754 Cov.: 33

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0463

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.313

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.313 AC: 47633 AN: 152034 Hom.: 7752 Cov.: 33 AF XY: 0.307 AC XY: 22829 AN XY: 74276

African (AFR) AF: 0.352 AC: 14609 AN: 41452

American (AMR) AF: 0.247 AC: 3777 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1031 AN: 3468

East Asian (EAS) AF: 0.0466 AC: 242 AN: 5194

South Asian (SAS) AF: 0.255 AC: 1227 AN: 4818

European-Finnish (FIN) AF: 0.291 AC: 3069 AN: 10552

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22706 AN: 67944

Other (OTH) AF: 0.309 AC: 652 AN: 2110

Alfa AF: 0.323 Hom.: 33255

Bravo AF: 0.305

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	16
DANN	Benign	0.70
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10492025; hg19: chr12-113273050;