rs2240193

Positions:

• chr12-112897856-C-A
• chr12-112897856-C-T

Variant summary

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

The NM_001143854.2(RPH3A):​c.*1076C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,892 control chromosomes in the GnomAD database, including 2,161 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 0.14 (2161 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: RPH3A NM_001143854.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPH3A	NM_001143854.2	c.*1076C>A		3_prime_UTR_variant	22/22	ENST00000389385.9	NP_001137326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPH3A	ENST00000389385.9	c.*1076C>A		3_prime_UTR_variant	22/22	1	NM_001143854.2	ENSP00000374036	P3
RPH3A	ENST00000549913.6	n.4163C>A		non_coding_transcript_exon_variant	14/14	1
RPH3A	ENST00000415485.7	c.*1076C>A		3_prime_UTR_variant	21/21	5		ENSP00000405357	P3
RPH3A	ENST00000549324.1	n.1668C>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21837 AN: 151734 Hom.: 2151 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0655

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.100 AC: 4 AN: 40 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 3 AN XY: 18

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.111

GnomAD4 genome AF: 0.144 AC: 21889 AN: 151852 Hom.: 2161 Cov.: 32 AF XY: 0.150 AC XY: 11169 AN XY: 74238

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.0735

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.0655

Gnomad4 OTH AF: 0.143

Alfa AF: 0.0715 Hom.: 645

Bravo AF: 0.153

Asia WGS AF: 0.175 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.2
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2240193; hg19: chr12-113335661;