chr12-112578749-C-T

Variant names:

• chr12-112578749-C-T
• rs10850061
• NM_001347952.2:c.-140+3430C>T

Variant summary

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

The NM_001347952.2(RPH3A):​c.-140+3430C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,120 control chromosomes in the GnomAD database, including 3,052 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 (3052 hom., cov: 32)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 14 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 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.-140+3430C>T		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.-140+3430C>T		intron	N/A	ENSP00000440384.2	Q9Y2J0-1
	RPH3A	ENST00000942157.1		c.-314+3430C>T		intron	N/A	ENSP00000612216.1
	RPH3A	ENST00000942158.1		c.-130+3430C>T		intron	N/A	ENSP00000612217.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22477 AN: 152000 Hom.: 3059 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0826

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0836

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.148 AC: 22477 AN: 152120 Hom.: 3052 Cov.: 32 AF XY: 0.153 AC XY: 11367 AN XY: 74378

African (AFR) AF: 0.176 AC: 7319 AN: 41492

American (AMR) AF: 0.205 AC: 3127 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 215 AN: 3470

East Asian (EAS) AF: 0.790 AC: 4091 AN: 5178

South Asian (SAS) AF: 0.168 AC: 809 AN: 4812

European-Finnish (FIN) AF: 0.0826 AC: 874 AN: 10582

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0837 AC: 5688 AN: 67992

Other (OTH) AF: 0.146 AC: 309 AN: 2112

Alfa AF: 0.110 Hom.: 6665

Bravo AF: 0.168

Asia WGS AF: 0.417 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.61
PhyloP100		-1.4
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: rs10850061; hg19: chr12-113016553;