12-112690085-T-C

Variant names:

• chr12-112690085-T-C
• rs10492019
• NM_001347952.2:c.-139-102058T>C

Variant summary

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

The NM_001347952.2(RPH3A):​c.-139-102058T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,234 control chromosomes in the GnomAD database, including 3,586 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 0.13 (3586 hom., cov: 33)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.815
• 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):

• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPH3A	NM_001347952.2	c.-139-102058T>C		intron_variant	Intron 1 of 21		NP_001334881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3A	ENST00000543106.6	c.-139-102058T>C		intron_variant	Intron 1 of 21	2		ENSP00000440384.2
RPH3A	ENST00000551593.5	c.-19+114766T>C		intron_variant	Intron 1 of 6	4		ENSP00000446780.1
RPH3A	ENST00000547840.5	c.-140+98485T>C		intron_variant	Intron 1 of 6	4		ENSP00000450382.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19714 AN: 152114 Hom.: 3562 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.0258

Gnomad SAS AF: 0.0542

Gnomad FIN AF: 0.00442

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.0860

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

GnomAD4 genome AF: 0.130 AC: 19800 AN: 152234 Hom.: 3586 Cov.: 33 AF XY: 0.126 AC XY: 9392 AN XY: 74446

African (AFR) AF: 0.404 AC: 16764 AN: 41478

American (AMR) AF: 0.109 AC: 1662 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

East Asian (EAS) AF: 0.0260 AC: 135 AN: 5190

South Asian (SAS) AF: 0.0541 AC: 261 AN: 4828

European-Finnish (FIN) AF: 0.00442 AC: 47 AN: 10622

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0104 AC: 706 AN: 68036

Other (OTH) AF: 0.0851 AC: 180 AN: 2114

Alfa AF: 0.0578 Hom.: 2201

Bravo AF: 0.151

Asia WGS AF: 0.0700 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.9
DANN	Benign	0.62
PhyloP100		0.81
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: rs10492019; hg19: chr12-113127890;