rs12942009

Variant names:

• chr17-353665-C-T
• rs12942009
• ENST00000907490.1:c.-154-4290G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000573780.5(RPH3AL):​c.-36-26086G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.16 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: RPH3AL ENST00000573780.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 0 publications found

Genes affected

RPH3AL (HGNC:10296): (rabphilin 3A like (without C2 domains)) The protein encoded by this gene plays a direct regulatory role in calcium-ion-dependent exocytosis in both endocrine and exocrine cells and plays a key role in insulin secretion by pancreatic cells. This gene is likely a tumor suppressor. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jun 2010]

RPH3AL-AS2 (HGNC:56089): (RPH3AL antisense RNA 2)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000573780.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3AL	ENST00000907490.1		c.-154-4290G>A		intron	N/A	ENSP00000577549.1
	RPH3AL	ENST00000907489.1		c.-36-26086G>A		intron	N/A	ENSP00000577548.1
	RPH3AL	ENST00000913661.1		c.-153-25837G>A		intron	N/A	ENSP00000583720.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 3122 AN: 20070 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0818

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.181

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.155 AC: 3125 AN: 20104 Hom.: 0 Cov.: 0 AF XY: 0.160 AC XY: 1580 AN XY: 9852

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.104 AC: 664 AN: 6360

American (AMR) AF: 0.174 AC: 344 AN: 1974

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 61 AN: 416

East Asian (EAS) AF: 0.0831 AC: 54 AN: 650

South Asian (SAS) AF: 0.250 AC: 123 AN: 492

European-Finnish (FIN) AF: 0.187 AC: 225 AN: 1204

Middle Eastern (MID) AF: 0.139 AC: 5 AN: 36

European-Non Finnish (NFE) AF: 0.183 AC: 1568 AN: 8556

Other (OTH) AF: 0.181 AC: 55 AN: 304

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.419 Hom.: 168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.6
DANN	Benign	0.61
PhyloP100		-0.089

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12942009;

hg19: chr17-203456;