NM_001347952.2:c.-139-71110G>A

Variant names:

• chr12-112721033-G-A
• rs7312122
• NM_001347952.2:c.-139-71110G>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.-139-71110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,010 control chromosomes in the GnomAD database, including 1,813 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 0.15 (1813 hom., cov: 32)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• Publications: 3 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 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.-139-71110G>A		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.-139-71110G>A		intron	N/A	ENSP00000440384.2	Q9Y2J0-1
	RPH3A	ENST00000942157.1		c.-139-71110G>A		intron	N/A	ENSP00000612216.1
	RPH3A	ENST00000942158.1		c.-19+69206G>A		intron	N/A	ENSP00000612217.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22842 AN: 151892 Hom.: 1791 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.151 AC: 22921 AN: 152010 Hom.: 1813 Cov.: 32 AF XY: 0.149 AC XY: 11100 AN XY: 74304

African (AFR) AF: 0.189 AC: 7836 AN: 41424

American (AMR) AF: 0.148 AC: 2255 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3468

East Asian (EAS) AF: 0.0952 AC: 493 AN: 5176

South Asian (SAS) AF: 0.204 AC: 979 AN: 4810

European-Finnish (FIN) AF: 0.0907 AC: 960 AN: 10584

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9582 AN: 67964

Other (OTH) AF: 0.142 AC: 300 AN: 2112

Alfa AF: 0.142 Hom.: 2459

Bravo AF: 0.153

Asia WGS AF: 0.157 AC: 548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.4
DANN	Benign	0.41
PhyloP100		-0.16
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: rs7312122; hg19: chr12-113158838;