rs10492018

Variant names:

• chr12-112689599-G-A
• rs10492018
• NM_001347952.2:c.-139-102544G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-112689599-G-A
• chr12-112689599-G-T

Variant summary

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

The NM_001347952.2(RPH3A):​c.-139-102544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,972 control chromosomes in the GnomAD database, including 8,092 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 0.32 (8092 hom., cov: 32)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPH3A	NM_001347952.2	c.-139-102544G>A		intron_variant	Intron 1 of 21		NP_001334881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3A	ENST00000543106.6	c.-139-102544G>A		intron_variant	Intron 1 of 21	2		ENSP00000440384.2
RPH3A	ENST00000551593.5	c.-19+114280G>A		intron_variant	Intron 1 of 6	4		ENSP00000446780.1
RPH3A	ENST00000547840.5	c.-140+97999G>A		intron_variant	Intron 1 of 6	4		ENSP00000450382.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48581 AN: 151854 Hom.: 8070 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.320 AC: 48657 AN: 151972 Hom.: 8092 Cov.: 32 AF XY: 0.323 AC XY: 23979 AN XY: 74276

African (AFR) AF: 0.407 AC: 16851 AN: 41422

American (AMR) AF: 0.348 AC: 5311 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3466

East Asian (EAS) AF: 0.282 AC: 1458 AN: 5168

South Asian (SAS) AF: 0.291 AC: 1405 AN: 4820

European-Finnish (FIN) AF: 0.370 AC: 3904 AN: 10538

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18158 AN: 67982

Other (OTH) AF: 0.303 AC: 639 AN: 2106

Alfa AF: 0.313 Hom.: 1635

Bravo AF: 0.320

Asia WGS AF: 0.319 AC: 1109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.46
DANN	Benign	0.65
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10492018; hg19: chr12-113127404;