chr12-112897856-C-T

Variant names:

• chr12-112897856-C-T
• rs2240193
• NM_001143854.2:c.*1076C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001143854.2(RPH3A):​c.*1076C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: RPH3A NM_001143854.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 14 publications found

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):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, PanelApp Australia
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• congenital myasthenic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3A	NM_001143854.2	MANE Select	c.*1076C>T		3_prime_UTR	Exon 22 of 22	NP_001137326.1	Q9Y2J0-1
	RPH3A	NM_001347952.2		c.*1076C>T		3_prime_UTR	Exon 22 of 22	NP_001334881.1	Q9Y2J0-1
	RPH3A	NM_001347953.1		c.*1076C>T		3_prime_UTR	Exon 22 of 22	NP_001334882.1	Q9Y2J0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3A	ENST00000389385.9	TSL:1 MANE Select	c.*1076C>T		3_prime_UTR	Exon 22 of 22	ENSP00000374036.4	Q9Y2J0-1
	RPH3A	ENST00000549913.6	TSL:1	n.4163C>T		non_coding_transcript_exon	Exon 14 of 14
	RPH3A	ENST00000415485.7	TSL:5	c.*1076C>T		3_prime_UTR	Exon 21 of 21	ENSP00000405357.3	Q9Y2J0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.8
DANN	Benign	0.56
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs2240193; hg19: chr12-113335661;