rs1170052582

Variant names:

• chr17-215683-G-A
• rs1170052582
• NM_006987.4:c.847C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-215683-G-A
• chr17-215683-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006987.4(RPH3AL):​c.847C>T​(p.Pro283Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPH3AL NM_006987.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.577

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09545672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPH3AL	NM_006987.4	c.847C>T	p.Pro283Ser	missense_variant	Exon 9 of 10	ENST00000331302.12	NP_008918.1
RPH3AL	NM_001190411.2	c.847C>T	p.Pro283Ser	missense_variant	Exon 8 of 9		NP_001177340.1
RPH3AL	NM_001190412.2	c.760C>T	p.Pro254Ser	missense_variant	Exon 8 of 9		NP_001177341.1
RPH3AL	NM_001190413.2	c.760C>T	p.Pro254Ser	missense_variant	Exon 7 of 8		NP_001177342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3AL	ENST00000331302.12	c.847C>T	p.Pro283Ser	missense_variant	Exon 9 of 10	2	NM_006987.4	ENSP00000328977.7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1123356 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 532738

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T;T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.42	T;.;.;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.095	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.20	.;.;.;N
REVEL	Benign	0.059
Sift	Benign	0.13	.;.;.;T
Sift4G	Benign	0.41	T;T;T;T
Polyphen		0.44	B;B;P;P
Vest4		0.22
MVP		0.33
MPC		0.32
ClinPred		0.17	T
GERP RS		2.7
Varity_R		0.022
gMVP		0.083

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1170052582; hg19: chr17-65474;