12-112831607-A-G

Variant summary

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

The NM_001143854.2(RPH3A):​c.71+3218A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 241,912 control chromosomes in the GnomAD database, including 15,618 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 0.36 ( 9831 hom., cov: 30)
Exomes 𝑓: 0.32 ( 5787 hom. )

Consequence

RPH3A
NM_001143854.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.643
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]

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=-0.76).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPH3ANM_001143854.2 linkc.71+3218A>G intron_variant Intron 3 of 21 ENST00000389385.9 NP_001137326.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPH3AENST00000389385.9 linkc.71+3218A>G intron_variant Intron 3 of 21 1 NM_001143854.2 ENSP00000374036.4 Q9Y2J0-1

Frequencies

GnomAD3 genomes
AF:
0.356
AC:
53819
AN:
151258
Hom.:
9825
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.288
Gnomad AMI
AF:
0.460
Gnomad AMR
AF:
0.381
Gnomad ASJ
AF:
0.422
Gnomad EAS
AF:
0.551
Gnomad SAS
AF:
0.379
Gnomad FIN
AF:
0.338
Gnomad MID
AF:
0.332
Gnomad NFE
AF:
0.372
Gnomad OTH
AF:
0.380
GnomAD4 exome
AF:
0.322
AC:
29191
AN:
90534
Hom.:
5787
AF XY:
0.325
AC XY:
16610
AN XY:
51082
show subpopulations
Gnomad4 AFR exome
AF:
0.236
Gnomad4 AMR exome
AF:
0.356
Gnomad4 ASJ exome
AF:
0.384
Gnomad4 EAS exome
AF:
0.483
Gnomad4 SAS exome
AF:
0.322
Gnomad4 FIN exome
AF:
0.291
Gnomad4 NFE exome
AF:
0.316
Gnomad4 OTH exome
AF:
0.312
GnomAD4 genome
AF:
0.356
AC:
53861
AN:
151378
Hom.:
9831
Cov.:
30
AF XY:
0.357
AC XY:
26362
AN XY:
73920
show subpopulations
Gnomad4 AFR
AF:
0.288
Gnomad4 AMR
AF:
0.380
Gnomad4 ASJ
AF:
0.422
Gnomad4 EAS
AF:
0.550
Gnomad4 SAS
AF:
0.379
Gnomad4 FIN
AF:
0.338
Gnomad4 NFE
AF:
0.372
Gnomad4 OTH
AF:
0.386
Alfa
AF:
0.375
Hom.:
16039
Bravo
AF:
0.360
Asia WGS
AF:
0.474
AC:
1647
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
5.2
DANN
Benign
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

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

Other links and lift over

dbSNP: rs10492024; hg19: chr12-113269412; API