chr17-279666-C-T

Variant names:

• chr17-279666-C-T
• rs9788983
• NM_006987.4:c.438+2102G>A

Variant summary

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

The NM_006987.4(RPH3AL):​c.438+2102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,950 control chromosomes in the GnomAD database, including 13,320 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 0.41 (13320 hom., cov: 32)
• Consequence: RPH3AL NM_006987.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 7 publications found

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]

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 (EAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006987.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3AL	NM_006987.4	MANE Select	c.438+2102G>A		intron	N/A	NP_008918.1	Q9UNE2-1
	RPH3AL	NM_001190411.2		c.438+2102G>A		intron	N/A	NP_001177340.1	Q9UNE2-1
	RPH3AL	NM_001190412.2		c.352-32381G>A		intron	N/A	NP_001177341.1	Q9UNE2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3AL	ENST00000331302.12	TSL:2 MANE Select	c.438+2102G>A		intron	N/A	ENSP00000328977.7	Q9UNE2-1
	RPH3AL	ENST00000323434.12	TSL:1	c.352-32381G>A		intron	N/A	ENSP00000319210.8	Q9UNE2-2
	RPH3AL	ENST00000953554.1		c.438+2102G>A		intron	N/A	ENSP00000623613.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62179 AN: 151832 Hom.: 13300 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.410 AC: 62239 AN: 151950 Hom.: 13320 Cov.: 32 AF XY: 0.411 AC XY: 30523 AN XY: 74258

African (AFR) AF: 0.356 AC: 14752 AN: 41428

American (AMR) AF: 0.459 AC: 7015 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1325 AN: 3466

East Asian (EAS) AF: 0.733 AC: 3787 AN: 5168

South Asian (SAS) AF: 0.512 AC: 2466 AN: 4820

European-Finnish (FIN) AF: 0.371 AC: 3903 AN: 10532

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27484 AN: 67940

Other (OTH) AF: 0.437 AC: 922 AN: 2108

Alfa AF: 0.412 Hom.: 33261

Bravo AF: 0.416

Asia WGS AF: 0.620 AC: 2153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.42
PhyloP100		0.071
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9788983; hg19: chr17-129457; COSMIC: COSV58740000; COSMIC: COSV58740000;