17-353140-C-CA

Position:

• chr17-353140-C-CA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000573780.5(RPH3AL):​c.-36-25562_-36-25561insT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.97 (71264 hom., cov: 0)
  • Exomes 𝑓: 1.0 (5 hom.)
• Consequence: RPH3AL ENST00000573780.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.353140_353141insA		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPH3AL	ENST00000573780.5	c.-36-25562_-36-25561insT		intron_variant		4		ENSP00000459992.1
RPH3AL	ENST00000575130.5	c.-212-19207_-212-19206insT		intron_variant		4		ENSP00000460171.1
RPH3AL-AS2	ENST00000572499.1	n.225+278_225+279insA		intron_variant		3
RPH3AL	ENST00000323434.12	c.-642_-641insT		upstream_gene_variant		1		ENSP00000319210.8

Frequencies

GnomAD3 genomes AF: 0.966 AC: 146995 AN: 152112 Hom.: 71215 Cov.: 0

Gnomad AFR AF: 0.886

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.976

GnomAD4 exome AF: 1.00 AC: 10 AN: 10 Hom.: 5 Cov.: 0 AF XY: 1.00 AC XY: 8 AN XY: 8

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.966 AC: 147104 AN: 152230 Hom.: 71264 Cov.: 0 AF XY: 0.967 AC XY: 71978 AN XY: 74448

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.985

Gnomad4 ASJ AF: 0.979

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.976

Alfa AF: 0.978 Hom.: 7827

Asia WGS AF: 0.992 AC: 3450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11383870; hg19: chr17-202931;