rs2240191

Variant names:

• chr12-112897926-G-T
• rs2240191
• NM_001143854.2:c.*1146G>T

Variant summary

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

The NM_001143854.2(RPH3A):​c.*1146G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,200 control chromosomes in the GnomAD database, including 6,230 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 0.26 (6230 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: RPH3A NM_001143854.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPH3A	NM_001143854.2	c.*1146G>T		3_prime_UTR_variant	Exon 22 of 22	ENST00000389385.9	NP_001137326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3A	ENST00000389385.9	c.*1146G>T		3_prime_UTR_variant	Exon 22 of 22	1	NM_001143854.2	ENSP00000374036.4
RPH3A	ENST00000549913.6	n.4233G>T		non_coding_transcript_exon_variant	Exon 14 of 14	1
RPH3A	ENST00000415485.7	c.*1146G>T		3_prime_UTR_variant	Exon 21 of 21	5		ENSP00000405357.3
RPH3A	ENST00000549324.1	n.1738G>T		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.263 AC: 40008 AN: 151956 Hom.: 6216 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.175 AC: 22 AN: 126 Hom.: 0 Cov.: 0 AF XY: 0.149 AC XY: 14 AN XY: 94

Gnomad4 AFR exome AF: 0.500 AC: 2 AN: 4

Gnomad4 AMR exome AC: 0 AN: 0

Gnomad4 ASJ exome AC: 0 AN: 0

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 2

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 2

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 2

Gnomad4 NFE exome AF: 0.170 AC: 18 AN: 106

Gnomad4 Remaining exome AF: 0.125 AC: 1 AN: 8

GnomAD4 genome AF: 0.263 AC: 40071 AN: 152074 Hom.: 6230 Cov.: 32 AF XY: 0.262 AC XY: 19450 AN XY: 74338

Gnomad4 AFR AF: 0.411 AC: 0.411424 AN: 0.411424

Gnomad4 AMR AF: 0.317 AC: 0.316706 AN: 0.316706

Gnomad4 ASJ AF: 0.216 AC: 0.216427 AN: 0.216427

Gnomad4 EAS AF: 0.445 AC: 0.445134 AN: 0.445134

Gnomad4 SAS AF: 0.196 AC: 0.195896 AN: 0.195896

Gnomad4 FIN AF: 0.152 AC: 0.15219 AN: 0.15219

Gnomad4 NFE AF: 0.174 AC: 0.174189 AN: 0.174189

Gnomad4 OTH AF: 0.272 AC: 0.271996 AN: 0.271996

Alfa AF: 0.209 Hom.: 6185

Bravo AF: 0.288

Asia WGS AF: 0.306 AC: 1063 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.15
DANN	Benign	0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2240191; hg19: chr12-113335731;