12-112766236-A-G

Variant names:

• chr12-112766236-A-G
• rs7132204
• NM_001347952.2:c.-139-25907A>G

Variant summary

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

The NM_001347952.2(RPH3A):​c.-139-25907A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,942 control chromosomes in the GnomAD database, including 19,110 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 0.49 (19110 hom., cov: 32)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 2 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 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.-139-25907A>G		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.-139-25907A>G		intron	N/A	ENSP00000440384.2	Q9Y2J0-1
	RPH3A	ENST00000942157.1		c.-139-25907A>G		intron	N/A	ENSP00000612216.1
	RPH3A	ENST00000942158.1		c.-18-62065A>G		intron	N/A	ENSP00000612217.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74136 AN: 151824 Hom.: 19086 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.488 AC: 74214 AN: 151942 Hom.: 19110 Cov.: 32 AF XY: 0.489 AC XY: 36269 AN XY: 74232

African (AFR) AF: 0.646 AC: 26770 AN: 41440

American (AMR) AF: 0.377 AC: 5750 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1224 AN: 3470

East Asian (EAS) AF: 0.697 AC: 3590 AN: 5150

South Asian (SAS) AF: 0.572 AC: 2751 AN: 4810

European-Finnish (FIN) AF: 0.433 AC: 4563 AN: 10546

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.415 AC: 28177 AN: 67952

Other (OTH) AF: 0.460 AC: 971 AN: 2110

Alfa AF: 0.435 Hom.: 2713

Bravo AF: 0.490

Asia WGS AF: 0.607 AC: 2115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.29
PhyloP100		-1.7
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: rs7132204; hg19: chr12-113204041;