rs233722

Variant names:

• chr12-112593670-G-A
• rs233722
• NM_001347952.2:c.-140+18351G>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+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
• Publications: 17 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=-0.94).
• 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 rank	MANE	Protein	UniProt
RPH3A	NM_001347952.2	c.-140+18351G>A		intron_variant	Intron 1 of 21		NP_001334881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3A	ENST00000543106.6	c.-140+18351G>A		intron_variant	Intron 1 of 21	2		ENSP00000440384.2
RPH3A	ENST00000551593.5	c.-19+18351G>A		intron_variant	Intron 1 of 6	4		ENSP00000446780.1
RPH3A	ENST00000547840.5	c.-140+2070G>A		intron_variant	Intron 1 of 6	4		ENSP00000450382.1

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

African (AFR) AF: 0.412 AC: 17103 AN: 41498

American (AMR) AF: 0.552 AC: 8440 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1287 AN: 3468

East Asian (EAS) AF: 0.354 AC: 1830 AN: 5176

South Asian (SAS) AF: 0.701 AC: 3377 AN: 4816

European-Finnish (FIN) AF: 0.684 AC: 7233 AN: 10578

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40310 AN: 67970

Other (OTH) AF: 0.535 AC: 1130 AN: 2114

Alfa AF: 0.572 Hom.: 52942

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
PhyloP100		-0.31
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: rs233722; hg19: chr12-113031474;