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

Variant summary

Our verdict is Benign. The variant received -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

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: G2P
congenital myasthenic syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

RPH3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143854.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPH3A	NM_001143854.2	MANE Select	c.*1670C>T	3_prime_UTR	Exon 22 of 22	NP_001137326.1	Q9Y2J0-1
RPH3A	NM_001347952.2		c.*1670C>T	3_prime_UTR	Exon 22 of 22	NP_001334881.1	Q9Y2J0-1
RPH3A	NM_001347953.1		c.*1670C>T	3_prime_UTR	Exon 22 of 22	NP_001334882.1	Q9Y2J0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPH3A	ENST00000389385.9	TSL:1 MANE Select	c.*1670C>T	3_prime_UTR	Exon 22 of 22	ENSP00000374036.4	Q9Y2J0-1
RPH3A	ENST00000549913.6	TSL:1	n.4757C>T	non_coding_transcript_exon	Exon 14 of 14
RPH3A	ENST00000415485.7	TSL:5	c.*1670C>T	3_prime_UTR	Exon 21 of 21	ENSP00000405357.3	Q9Y2J0-1

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

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.133

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0397

AC:

6052

AN:

152278

Hom.:

141

Cov.:

AF XY:

0.0423

AC XY:

3147

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0413

AC:

1716

AN:

41560

American (AMR)

AF:

0.0252

AC:

385

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0746

AC:

259

AN:

3470

East Asian (EAS)

AF:

0.00251

AC:

AN:

5188

South Asian (SAS)

AF:

0.0847

AC:

408

AN:

4818

European-Finnish (FIN)

AF:

0.0579

AC:

614

AN:

10612

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0367

AC:

2493

AN:

68012

Other (OTH)

AF:

0.0450

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

316

632

948

1264

1580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0394

Hom.:

Bravo

AF:

0.0354

Asia WGS

AF:

0.0730

AC:

254

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.067

(source)

DANN

Benign

0.46

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over