12-112871384-T-C

Position:

• chr12-112871384-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPH3A	NM_001143854.2	c.796+1345T>C		intron_variant		ENST00000389385.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPH3A	ENST00000389385.9	c.796+1345T>C		intron_variant		1	NM_001143854.2	P3

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

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.499

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs2384069; hg19: chr12-113309189;