rs233716

Variant names:

• chr12-112602139-C-T
• rs233716
• NM_001347952.2:c.-140+26820C>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.-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
• 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):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, PanelApp Australia
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.681 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3A	NM_001347952.2		c.-140+26820C>T		intron	N/A	NP_001334881.1	Q9Y2J0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3A	ENST00000543106.6	TSL:2	c.-140+26820C>T		intron	N/A	ENSP00000440384.2	Q9Y2J0-1
	RPH3A	ENST00000942157.1		c.-313-10621C>T		intron	N/A	ENSP00000612216.1
	RPH3A	ENST00000942158.1		c.-130+26820C>T		intron	N/A	ENSP00000612217.1

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

African (AFR) AF: 0.516 AC: 21361 AN: 41386

American (AMR) AF: 0.652 AC: 9962 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1287 AN: 3464

East Asian (EAS) AF: 0.370 AC: 1912 AN: 5162

South Asian (SAS) AF: 0.700 AC: 3369 AN: 4810

European-Finnish (FIN) AF: 0.690 AC: 7293 AN: 10568

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40516 AN: 67946

Other (OTH) AF: 0.558 AC: 1177 AN: 2110

Alfa AF: 0.581 Hom.: 113408

Bravo AF: 0.566

Asia WGS AF: 0.580 AC: 2018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.41
DANN	Benign	0.43
PhyloP100		-0.57
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: rs233716; hg19: chr12-113039943;