17-353102-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000572499.1(RPH3AL-AS2):n.225+240C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.964 in 152,302 control chromosomes in the GnomAD database, including 70,901 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 0.96 (70897 hom., cov: 33)
  • Exomes 𝑓: 1.0 (4 hom.)
• Consequence: RPH3AL-AS2 ENST00000572499.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPH3AL-AS2	ENST00000572499.1	n.225+240C>T		intron_variant, non_coding_transcript_variant		3
RPH3AL	ENST00000573780.5	c.-36-25523G>A		intron_variant		4
RPH3AL	ENST00000575130.5	c.-212-19168G>A		intron_variant		4
RPH3AL	ENST00000323434.12			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.964 AC: 146650 AN: 152176 Hom.: 70848 Cov.: 33

Gnomad AFR AF: 0.885

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.996

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.971

GnomAD4 exome AF: 1.00 AC: 8 AN: 8 Hom.: 4 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.964 AC: 146759 AN: 152294 Hom.: 70897 Cov.: 33 AF XY: 0.964 AC XY: 71801 AN XY: 74478

Gnomad4 AFR AF: 0.885

Gnomad4 AMR AF: 0.966

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.996

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.972

Alfa AF: 0.978 Hom.: 10344

Bravo AF: 0.957

Asia WGS AF: 0.977 AC: 3397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.59
Dann	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7215343; hg19: chr17-202893;