rs3803064

chr12-112735689-G-Achr12-112735689-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPH3A	NM_001347952.2	c.-139-56454G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPH3A	ENST00000543106.6	c.-139-56454G>A		intron_variant		2		P3
RPH3A	ENST00000546426.5	c.-139-56454G>A		intron_variant		4
RPH3A	ENST00000546703.5	c.-139-56454G>A		intron_variant		5

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

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.403

Alfa AF: 0.404 Hom.: 19625

Bravo AF: 0.375

Asia WGS AF: 0.525 AC: 1825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.50
Dann	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3803064; hg19: chr12-113173494;