rs233722

Positions:

• chr12-112593670-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001347952.2(RPH3A):​c.-140+18351G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,108 control chromosomes in the GnomAD database, including 22,732 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 0.54 (22732 hom., cov: 32)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPH3A	NM_001347952.2	c.-140+18351G>A		intron_variant			NP_001334881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPH3A	ENST00000543106.6	c.-140+18351G>A		intron_variant		2		ENSP00000440384	P3
RPH3A	ENST00000546426.5	c.-369+18351G>A		intron_variant		4		ENSP00000447639
RPH3A	ENST00000546703.5	c.-258+18351G>A		intron_variant		5		ENSP00000446556

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81349 AN: 151990 Hom.: 22715 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.535 AC: 81400 AN: 152108 Hom.: 22732 Cov.: 32 AF XY: 0.542 AC XY: 40293 AN XY: 74354

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.535

Alfa AF: 0.574 Hom.: 36140

Bravo AF: 0.514

Asia WGS AF: 0.536 AC: 1866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs233722; hg19: chr12-113031474;