12-112866785-C-G

Variant names:

• chr12-112866785-C-G
• NM_001143854.2:c.389C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001143854.2(RPH3A):​c.389C>G​(p.Thr130Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,457,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: RPH3A NM_001143854.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18162492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPH3A	NM_001143854.2	c.389C>G	p.Thr130Ser	missense_variant	Exon 7 of 22	ENST00000389385.9	NP_001137326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3A	ENST00000389385.9	c.389C>G	p.Thr130Ser	missense_variant	Exon 7 of 22	1	NM_001143854.2	ENSP00000374036.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1457296 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 724508

Gnomad4 AFR exome AF: 0.00

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: 0.00000541

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T;T;T;T;T;.;T;.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.65	T;T;T;.;T;T;.;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.44	N;.;.;N;.;.;N;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.74	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.17	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.56	T;T;T;T;T;T;T;T;T
Polyphen		0.0040	B;.;.;B;.;B;B;.;B
Vest4		0.40
MutPred		0.55		Gain of catalytic residue at K125 (P = 6e-04);Gain of catalytic residue at K125 (P = 6e-04);Gain of catalytic residue at K125 (P = 6e-04);Gain of catalytic residue at K125 (P = 6e-04);.;.;Gain of catalytic residue at K125 (P = 6e-04);Gain of catalytic residue at K125 (P = 6e-04);.;
MVP		0.38
MPC		0.25
ClinPred		0.39	T
GERP RS		3.8
Varity_R		0.096
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-113304590;