17-353576-C-T

Variant names:

• chr17-353576-C-T
• rs9907777
• ENST00000573780.5:c.-36-25997G>A

Variant summary

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

The ENST00000573780.5(RPH3AL):​c.-36-25997G>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 0.23 (195 hom., cov: 0)
• Consequence: RPH3AL ENST00000573780.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

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	ENST00000573780.5	c.-36-25997G>A		intron_variant	Intron 1 of 4	4		ENSP00000459992.1
RPH3AL	ENST00000575130.5	c.-212-19642G>A		intron_variant	Intron 1 of 4	4		ENSP00000460171.1
RPH3AL-AS2	ENST00000572499.1	n.225+714C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.229 AC: 5510 AN: 24086 Hom.: 191 Cov.: 0

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.147

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.229 AC: 5528 AN: 24130 Hom.: 195 Cov.: 0 AF XY: 0.240 AC XY: 2834 AN XY: 11812

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.204

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9907777; hg19: chr17-203367;