12-112578749-C-T

Variant names:

• chr12-112578749-C-T
• rs10850061
• NM_001347952.2:c.-140+3430C>T

Variant summary

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

The NM_001347952.2(RPH3A):​c.-140+3430C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,120 control chromosomes in the GnomAD database, including 3,052 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 0.15 (3052 hom., cov: 32)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPH3A	NM_001347952.2	c.-140+3430C>T		intron_variant	Intron 1 of 21		NP_001334881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3A	ENST00000543106.6	c.-140+3430C>T		intron_variant	Intron 1 of 21	2		ENSP00000440384.2
RPH3A	ENST00000551593.5	c.-19+3430C>T		intron_variant	Intron 1 of 6	4		ENSP00000446780.1
RPH3A	ENST00000548197.5	c.-140+8205C>T		intron_variant	Intron 1 of 5	4		ENSP00000446570.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22477 AN: 152000 Hom.: 3059 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0826

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0836

Gnomad OTH AF: 0.146

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.148 AC: 22477 AN: 152120 Hom.: 3052 Cov.: 32 AF XY: 0.153 AC XY: 11367 AN XY: 74378

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.790

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.0826

Gnomad4 NFE AF: 0.0837

Gnomad4 OTH AF: 0.146

Alfa AF: 0.0998 Hom.: 2553

Bravo AF: 0.168

Asia WGS AF: 0.417 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10850061; hg19: chr12-113016553;