chr12-112887256-C-T

Variant names:

• chr12-112887256-C-T
• rs7958347
• NM_001143854.2:c.1437-541C>T

Variant summary

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

The NM_001143854.2(RPH3A):​c.1437-541C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,102 control chromosomes in the GnomAD database, including 14,835 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 0.44 (14835 hom., cov: 33)
• Consequence: RPH3A NM_001143854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 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.1437-541C>T		intron	N/A	NP_001137326.1	Q9Y2J0-1
	RPH3A	NM_001347952.2		c.1437-541C>T		intron	N/A	NP_001334881.1	Q9Y2J0-1
	RPH3A	NM_001347953.1		c.1437-541C>T		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.1437-541C>T		intron	N/A	ENSP00000374036.4	Q9Y2J0-1
	RPH3A	ENST00000551052.5	TSL:1	c.1425-541C>T		intron	N/A	ENSP00000448297.1	Q9Y2J0-2
	RPH3A	ENST00000549913.6	TSL:1	n.2439-541C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66166 AN: 151984 Hom.: 14817 Cov.: 33

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.435 AC: 66227 AN: 152102 Hom.: 14835 Cov.: 33 AF XY: 0.437 AC XY: 32496 AN XY: 74374

African (AFR) AF: 0.486 AC: 20166 AN: 41480

American (AMR) AF: 0.527 AC: 8061 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1554 AN: 3466

East Asian (EAS) AF: 0.591 AC: 3057 AN: 5176

South Asian (SAS) AF: 0.432 AC: 2087 AN: 4826

European-Finnish (FIN) AF: 0.327 AC: 3464 AN: 10578

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26304 AN: 67960

Other (OTH) AF: 0.442 AC: 934 AN: 2112

Alfa AF: 0.386 Hom.: 6254

Bravo AF: 0.460

Asia WGS AF: 0.513 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.84
PhyloP100		-0.016
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: rs7958347; hg19: chr12-113325061;