rs233716

chr12-112602139-C-T

Variant summary

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

The NM_001347952.2(RPH3A):c.-140+26820C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,922 control chromosomes in the GnomAD database, including 25,832 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 0.58 (25832 hom., cov: 30)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574

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=-0.98).
• 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	UniProt
RPH3A	NM_001347952.2	c.-140+26820C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPH3A	ENST00000543106.6	c.-140+26820C>T		intron_variant		2		P3
RPH3A	ENST00000546426.5	c.-368-15586C>T		intron_variant		4
RPH3A	ENST00000546703.5	c.-257-15586C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87469 AN: 151806 Hom.: 25793 Cov.: 30

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.576 AC: 87567 AN: 151922 Hom.: 25832 Cov.: 30 AF XY: 0.584 AC XY: 43365 AN XY: 74256

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.558

Alfa AF: 0.581 Hom.: 56875

Bravo AF: 0.566

Asia WGS AF: 0.580 AC: 2018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.41
Dann	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs233716; hg19: chr12-113039943;