12-112887256-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.1437-541C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,102 control chromosomes in the GnomAD database, including 14,835 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 0.44 (14835 hom., cov: 33)
• Consequence: RPH3A NM_001143854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPH3A	NM_001143854.2	c.1437-541C>T		intron_variant		ENST00000389385.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPH3A	ENST00000389385.9	c.1437-541C>T		intron_variant		1	NM_001143854.2	P3

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66166 AN: 151984 Hom.: 14817 Cov.: 33

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.435 AC: 66227 AN: 152102 Hom.: 14835 Cov.: 33 AF XY: 0.437 AC XY: 32496 AN XY: 74374

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.442

Alfa AF: 0.384 Hom.: 5508

Bravo AF: 0.460

Asia WGS AF: 0.513 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.8
Dann	Benign	0.84

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: rs7958347; hg19: chr12-113325061;