NM_001143854.2:c.796+1345T>C

Variant names:

• chr12-112871384-T-C
• rs2384069
• NM_001143854.2:c.796+1345T>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.796+1345T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,932 control chromosomes in the GnomAD database, including 19,497 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 0.50 (19497 hom., cov: 31)
• Consequence: RPH3A NM_001143854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3A	NM_001143854.2	MANE Select	c.796+1345T>C		intron	N/A	NP_001137326.1
	RPH3A	NM_001347952.2		c.796+1345T>C		intron	N/A	NP_001334881.1
	RPH3A	NM_001347953.1		c.796+1345T>C		intron	N/A	NP_001334882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3A	ENST00000389385.9	TSL:1 MANE Select	c.796+1345T>C		intron	N/A	ENSP00000374036.4
	RPH3A	ENST00000551052.5	TSL:1	c.784+1345T>C		intron	N/A	ENSP00000448297.1
	RPH3A	ENST00000549913.6	TSL:1	n.1798+1345T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75288 AN: 151816 Hom.: 19468 Cov.: 31

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.496 AC: 75372 AN: 151932 Hom.: 19497 Cov.: 31 AF XY: 0.496 AC XY: 36848 AN XY: 74256

African (AFR) AF: 0.631 AC: 26133 AN: 41412

American (AMR) AF: 0.566 AC: 8644 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1584 AN: 3464

East Asian (EAS) AF: 0.587 AC: 3041 AN: 5178

South Asian (SAS) AF: 0.444 AC: 2138 AN: 4818

European-Finnish (FIN) AF: 0.382 AC: 4028 AN: 10558

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28126 AN: 67912

Other (OTH) AF: 0.499 AC: 1052 AN: 2108

Alfa AF: 0.368 Hom.: 1479

Bravo AF: 0.524

Asia WGS AF: 0.545 AC: 1897 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	1.9
DANN	Benign	0.67
PhyloP100		0.041
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: rs2384069; hg19: chr12-113309189;