dbSNP rs12309946: RPH3A:c.*1670C>T (chr12-112898450-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001143854.2(RPH3A):c.*1670C>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 0.0398 in 152,316 control chromosomes in the GnomAD database, including 141 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 0.040 ( 141 hom., cov: 32)

Exomes 𝑓: 0.11 ( 0 hom. )

Consequence

RPH3A
NM_001143854.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.85

Variant links:

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]

RPH3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPH3A	NM_001143854.2 link	c.*1670C>T		3_prime_UTR_variant	Exon 22 of 22	ENST00000389385.9	NP_001137326.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RPH3A	ENST00000389385.9 link	c.*1670C>T	3_prime_UTR_variant	Exon 22 of 22	1	NM_001143854.2	ENSP00000374036.4	Q9Y2J0-1
RPH3A	ENST00000549913.6 link	n.4757C>T	non_coding_transcript_exon_variant	Exon 14 of 14	1
RPH3A	ENST00000415485.7 link	c.*1670C>T	3_prime_UTR_variant	Exon 21 of 21	5		ENSP00000405357.3	Q9Y2J0-1
RPH3A	ENST00000549324.1 link	n.2262C>T	non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.0397

AC:

6041

AN:

152160

Hom.:

140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0414

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0253

Gnomad ASJ

AF:

0.0746

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.0846

Gnomad FIN

AF:

0.0579

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0366

Gnomad OTH

AF:

0.0412

GnomAD4 exome

AF:

0.105

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0625

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0397

AC:

6052

AN:

152278

Hom.:

141

Cov.:

AF XY:

0.0423

AC XY:

3147

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0413

Gnomad4 AMR

AF:

0.0252

Gnomad4 ASJ

AF:

0.0746

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.0847

Gnomad4 FIN

AF:

0.0579

Gnomad4 NFE

AF:

0.0367

Gnomad4 OTH

AF:

0.0450

Alfa

AF:

0.0401

Hom.:

Bravo

AF:

0.0354

Asia WGS

AF:

0.0730

AC:

254

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.067

DANN

Benign

0.46

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over