17-353576-C-T

Variant names:

• chr17-353576-C-T
• rs9907777
• ENST00000717666.1:n.963C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000717666.1(RPH3AL-AS2):​n.963C>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 0.23 (195 hom., cov: 0)
• Consequence: RPH3AL-AS2 ENST00000717666.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• 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: Benign. The variant received -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-AS2	ENST00000717666.1	n.963C>T		non_coding_transcript_exon_variant	Exon 1 of 2
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

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

African (AFR) AF: 0.263 AC: 3015 AN: 11464

American (AMR) AF: 0.231 AC: 424 AN: 1838

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 68 AN: 430

East Asian (EAS) AF: 0.178 AC: 79 AN: 444

South Asian (SAS) AF: 0.327 AC: 134 AN: 410

European-Finnish (FIN) AF: 0.265 AC: 341 AN: 1286

Middle Eastern (MID) AF: 0.156 AC: 5 AN: 32

European-Non Finnish (NFE) AF: 0.175 AC: 1371 AN: 7816

Other (OTH) AF: 0.204 AC: 64 AN: 314

Alfa AF: 0.00 Hom.: 0

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
PhyloP100		-1.0
PromoterAI		-0.0092	Neutral

Splicing

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

Other links and lift over

dbSNP: rs9907777; hg19: chr17-203367;