rs74647838

Positions:

• chr12-112695096-G-A
• chr12-112695096-G-T

Variant summary

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

The NM_001347952.2(RPH3A):​c.-139-97047G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 170,458 control chromosomes in the GnomAD database, including 160 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 0.025 (160 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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]

MIR1302-1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPH3A	NM_001347952.2	c.-139-97047G>A		intron_variant			NP_001334881.1
MIR1302-1	NR_031631.1	n.81C>T		non_coding_transcript_exon_variant	1/1
MIR1302-1	unassigned_transcript_2075	n.7C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPH3A	ENST00000543106.6	c.-139-97047G>A		intron_variant		2		ENSP00000440384.2
RPH3A	ENST00000551593.5	c.-19+119777G>A		intron_variant		4		ENSP00000446780.1
RPH3A	ENST00000547840.5	c.-139-97047G>A		intron_variant		4		ENSP00000450382.1

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3765 AN: 152148 Hom.: 160 Cov.: 33

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.00664 AC: 156 AN: 23496 Hom.: 7 AF XY: 0.00534 AC XY: 56 AN XY: 10486

Gnomad AFR exome AF: 0.0793

Gnomad AMR exome AF: 0.0150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000808

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000220 AC: 4 AN: 18192 Hom.: 0 Cov.: 0 AF XY: 0.000230 AC XY: 2 AN XY: 8700

Gnomad4 AFR exome AF: 0.0256

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0247 AC: 3768 AN: 152266 Hom.: 160 Cov.: 33 AF XY: 0.0238 AC XY: 1773 AN XY: 74452

Gnomad4 AFR AF: 0.0854

Gnomad4 AMR AF: 0.0104

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0147 Hom.: 21

Bravo AF: 0.0285

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.87
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs74647838; hg19: chr12-113132901;