rs734400

Variant names:

• chr12-112795159-T-C
• rs734400
• NM_001143854.2:c.-19+2896T>C

Variant summary

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

The NM_001143854.2(RPH3A):​c.-19+2896T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 152,326 control chromosomes in the GnomAD database, including 147 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 0.022 (147 hom., cov: 32)
• Consequence: RPH3A NM_001143854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 0 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

ENSG00000306858 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143854.2. 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_001143854.2	MANE Select	c.-19+2896T>C		intron	N/A	NP_001137326.1	Q9Y2J0-1
	RPH3A	NM_001347952.2		c.-19+2896T>C		intron	N/A	NP_001334881.1	Q9Y2J0-1
	RPH3A	NM_001347953.1		c.-19+2896T>C		intron	N/A	NP_001334882.1	Q9Y2J0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3A	ENST00000389385.9	TSL:1 MANE Select	c.-19+2896T>C		intron	N/A	ENSP00000374036.4	Q9Y2J0-1
	RPH3A	ENST00000551052.5	TSL:1	c.-19+2896T>C		intron	N/A	ENSP00000448297.1	Q9Y2J0-2
	RPH3A	ENST00000415485.7	TSL:5	c.-19+2896T>C		intron	N/A	ENSP00000405357.3	Q9Y2J0-1

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3292 AN: 152208 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.0584

Gnomad FIN AF: 0.00527

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00967

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0217 AC: 3304 AN: 152326 Hom.: 147 Cov.: 32 AF XY: 0.0238 AC XY: 1774 AN XY: 74492

African (AFR) AF: 0.0116 AC: 484 AN: 41572

American (AMR) AF: 0.110 AC: 1679 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 38 AN: 3472

East Asian (EAS) AF: 0.00908 AC: 47 AN: 5178

South Asian (SAS) AF: 0.0584 AC: 282 AN: 4826

European-Finnish (FIN) AF: 0.00527 AC: 56 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00967 AC: 658 AN: 68038

Other (OTH) AF: 0.0284 AC: 60 AN: 2114

Alfa AF: 0.0117 Hom.: 64

Bravo AF: 0.0282

Asia WGS AF: 0.0390 AC: 137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.82
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs734400; hg19: chr12-113232964;