12-112690085-T-C

Position:

• chr12-112690085-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• 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/exons	MANE	Protein	UniProt
RPH3A	NM_001347952.2	c.-139-102058T>C		intron_variant			NP_001334881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPH3A	ENST00000543106.6	c.-139-102058T>C		intron_variant		2		ENSP00000440384.2
RPH3A	ENST00000551593.5	c.-19+114766T>C		intron_variant		4		ENSP00000446780.1
RPH3A	ENST00000547840.5	c.-140+98485T>C		intron_variant		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

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.0260

Gnomad4 SAS AF: 0.0541

Gnomad4 FIN AF: 0.00442

Gnomad4 NFE AF: 0.0104

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.0146 Hom.: 49

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10492019; hg19: chr12-113127890;