rs12942039

Variant names:

• chr17-353707-C-T
• rs12942039
• ENST00000717666.1:n.1094C>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.1094C>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 0.00046 (0 hom., cov: 28)
  • Failed GnomAD Quality Control
• Consequence: RPH3AL-AS2 ENST00000717666.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• 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=-0.88).

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.1094C>T		non_coding_transcript_exon_variant	Exon 1 of 2
RPH3AL	ENST00000573780.5	c.-36-26128G>A		intron_variant	Intron 1 of 4	4		ENSP00000459992.1
RPH3AL	ENST00000575130.5	c.-212-19773G>A		intron_variant	Intron 1 of 4	4		ENSP00000460171.1

Frequencies

GnomAD3 genomes AF: 0.000463 AC: 41 AN: 88566 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000389

Gnomad ASJ AF: 0.000544

Gnomad EAS AF: 0.000230

Gnomad SAS AF: 0.000880

Gnomad FIN AF: 0.000502

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000777

Gnomad OTH AF: 0.00

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: 0.000462 AC: 41 AN: 88674 Hom.: 0 Cov.: 28 AF XY: 0.000694 AC XY: 30 AN XY: 43202

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

African (AFR) AF: 0.000133 AC: 4 AN: 30016

American (AMR) AF: 0.000388 AC: 3 AN: 7732

Ashkenazi Jewish (ASJ) AF: 0.000544 AC: 1 AN: 1838

East Asian (EAS) AF: 0.000230 AC: 1 AN: 4348

South Asian (SAS) AF: 0.000880 AC: 2 AN: 2272

European-Finnish (FIN) AF: 0.000502 AC: 3 AN: 5978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 186

European-Non Finnish (NFE) AF: 0.000778 AC: 27 AN: 34726

Other (OTH) AF: 0.00 AC: 0 AN: 1144

⚠️ 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.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.56
PhyloP100		-0.013

Splicing

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

Other links and lift over

dbSNP: rs12942039; hg19: chr17-203498;