rs3803064

Variant names:

• chr12-112735689-G-A
• rs3803064
• NM_001347952.2:c.-139-56454G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-112735689-G-A
• chr12-112735689-G-C
• chr12-112735689-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.-139-56454G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,040 control chromosomes in the GnomAD database, including 11,687 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 0.39 (11687 hom., cov: 32)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.735
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347952.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3A	NM_001347952.2		c.-139-56454G>A		intron	N/A	NP_001334881.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3A	ENST00000543106.6	TSL:2	c.-139-56454G>A		intron	N/A	ENSP00000440384.2
	RPH3A	ENST00000551593.5	TSL:4	c.-18-92612G>A		intron	N/A	ENSP00000446780.1
	RPH3A	ENST00000547840.5	TSL:4	c.-139-56454G>A		intron	N/A	ENSP00000450382.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58644 AN: 151922 Hom.: 11691 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.386 AC: 58652 AN: 152040 Hom.: 11687 Cov.: 32 AF XY: 0.388 AC XY: 28854 AN XY: 74314

African (AFR) AF: 0.318 AC: 13182 AN: 41450

American (AMR) AF: 0.321 AC: 4914 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1241 AN: 3470

East Asian (EAS) AF: 0.675 AC: 3482 AN: 5160

South Asian (SAS) AF: 0.482 AC: 2320 AN: 4818

European-Finnish (FIN) AF: 0.431 AC: 4551 AN: 10556

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27692 AN: 67974

Other (OTH) AF: 0.403 AC: 850 AN: 2110

Alfa AF: 0.397 Hom.: 32233

Bravo AF: 0.375

Asia WGS AF: 0.525 AC: 1825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.50
DANN	Benign	0.41
PhyloP100		-0.73
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: rs3803064; hg19: chr12-113173494;