rs17824620

Variant names:

• chr12-112663189-C-A
• rs17824620
• NM_001347952.2:c.-140+87870C>A

Variant summary

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

The NM_001347952.2(RPH3A):​c.-140+87870C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,648 control chromosomes in the GnomAD database, including 6,059 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 0.26 (6059 hom., cov: 30)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 14 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 (AMR) allele frequency at 95% confidence interval = 0.319 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.-140+87870C>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.-140+87870C>A		intron	N/A	ENSP00000440384.2
	RPH3A	ENST00000942157.1		c.-140+50256C>A		intron	N/A	ENSP00000612216.1
	RPH3A	ENST00000942158.1		c.-19+11362C>A		intron	N/A	ENSP00000612217.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39603 AN: 151532 Hom.: 6054 Cov.: 30

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.261 AC: 39617 AN: 151648 Hom.: 6059 Cov.: 30 AF XY: 0.270 AC XY: 19994 AN XY: 74060

African (AFR) AF: 0.111 AC: 4589 AN: 41380

American (AMR) AF: 0.327 AC: 4966 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3466

East Asian (EAS) AF: 0.247 AC: 1264 AN: 5116

South Asian (SAS) AF: 0.270 AC: 1292 AN: 4792

European-Finnish (FIN) AF: 0.466 AC: 4887 AN: 10496

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.308 AC: 20935 AN: 67892

Other (OTH) AF: 0.270 AC: 570 AN: 2110

Alfa AF: 0.279 Hom.: 17398

Bravo AF: 0.242

Asia WGS AF: 0.281 AC: 976 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	4.3
DANN	Benign	0.67
PhyloP100		0.066
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: rs17824620; hg19: chr12-113100994;