rs12942009

Variant names:

• chr17-353665-C-T
• rs12942009
• ENST00000717666.1:n.1052C>T

Variant summary

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

The ENST00000717666.1(RPH3AL-AS2):​n.1052C>T variant causes a non coding transcript exon 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-AS2 ENST00000717666.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 0 publications found

Genes affected

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

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]

ACMG classification

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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3AL-AS2	ENST00000717666.1	n.1052C>T		non_coding_transcript_exon_variant	Exon 1 of 2
RPH3AL	ENST00000573780.5	c.-36-26086G>A		intron_variant	Intron 1 of 4	4		ENSP00000459992.1
RPH3AL	ENST00000575130.5	c.-212-19731G>A		intron_variant	Intron 1 of 4	4		ENSP00000460171.1

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 = 0.000000), 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 v4.3

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

Other links and lift over

dbSNP: rs12942009; hg19: chr17-203456;