rs3741982

Positions:

• chr12-112891176-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143854.2(RPH3A):​c.1775+173G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 695,880 control chromosomes in the GnomAD database, including 47,093 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 0.29 (8020 hom., cov: 32)
  • Exomes 𝑓: 0.37 (39073 hom.)
• Consequence: RPH3A NM_001143854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPH3A	NM_001143854.2	c.1775+173G>A		intron_variant		ENST00000389385.9	NP_001137326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPH3A	ENST00000389385.9	c.1775+173G>A		intron_variant		1	NM_001143854.2	ENSP00000374036	P3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44643 AN: 152032 Hom.: 8021 Cov.: 32

Gnomad AFR AF: 0.0790

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.372 AC: 202457 AN: 543728 Hom.: 39073 Cov.: 7 AF XY: 0.373 AC XY: 104939 AN XY: 281410

Gnomad4 AFR exome AF: 0.0729

Gnomad4 AMR exome AF: 0.365

Gnomad4 ASJ exome AF: 0.404

Gnomad4 EAS exome AF: 0.513

Gnomad4 SAS exome AF: 0.356

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.380

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome AF: 0.293 AC: 44648 AN: 152152 Hom.: 8020 Cov.: 32 AF XY: 0.296 AC XY: 22000 AN XY: 74380

Gnomad4 AFR AF: 0.0789

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.332

Alfa AF: 0.326 Hom.: 1422

Bravo AF: 0.293

Asia WGS AF: 0.399 AC: 1388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	15
DANN	Benign	0.50

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: rs3741982; hg19: chr12-113328981; COSMIC: COSV66993597; COSMIC: COSV66993597;