rs12949751

Variant names:

• chr17-353709-G-A
• rs12949751
• ENST00000907490.1:c.-154-4334C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000573780.5(RPH3AL):​c.-36-26130C>T 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 0.00028 (0 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: RPH3AL ENST00000573780.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 0 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]

RPH3AL-AS2 (HGNC:56089): (RPH3AL antisense RNA 2)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000573780.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3AL	ENST00000907490.1		c.-154-4334C>T		intron	N/A	ENSP00000577549.1
	RPH3AL	ENST00000907489.1		c.-36-26130C>T		intron	N/A	ENSP00000577548.1
	RPH3AL	ENST00000913661.1		c.-153-25881C>T		intron	N/A	ENSP00000583720.1

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 26 AN: 94308 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000642

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000121

Gnomad ASJ AF: 0.000513

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000799

Gnomad FIN AF: 0.000312

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000479

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000275 AC: 26 AN: 94424 Hom.: 0 Cov.: 29 AF XY: 0.000479 AC XY: 22 AN XY: 45974

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000639 AC: 2 AN: 31288

American (AMR) AF: 0.000121 AC: 1 AN: 8284

Ashkenazi Jewish (ASJ) AF: 0.000513 AC: 1 AN: 1948

East Asian (EAS) AF: 0.00 AC: 0 AN: 4452

South Asian (SAS) AF: 0.000800 AC: 2 AN: 2500

European-Finnish (FIN) AF: 0.000312 AC: 2 AN: 6412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 200

European-Non Finnish (NFE) AF: 0.000479 AC: 18 AN: 37608

Other (OTH) AF: 0.00 AC: 0 AN: 1236

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.50
PhyloP100		-0.083

Splicing

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

Other links and lift over

dbSNP: rs12949751; hg19: chr17-203500;