rs765780150

Variant names:

• chr17-219653-G-A
• rs765780150
• NM_006987.4:c.697C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-219653-G-A
• chr17-219653-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006987.4(RPH3AL):​c.697C>T​(p.Arg233Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000348 in 1,608,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R233Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000047 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: RPH3AL NM_006987.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.106
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.697C>T	p.Arg233Trp	missense	Exon 8 of 10	NP_008918.1	Q9UNE2-1
	RPH3AL	NM_001190411.2		c.697C>T	p.Arg233Trp	missense	Exon 7 of 9	NP_001177340.1	Q9UNE2-1
	RPH3AL	NM_001190412.2		c.610C>T	p.Arg204Trp	missense	Exon 7 of 9	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.697C>T	p.Arg233Trp	missense	Exon 8 of 10	ENSP00000328977.7	Q9UNE2-1
	RPH3AL	ENST00000323434.12	TSL:1	c.610C>T	p.Arg204Trp	missense	Exon 7 of 9	ENSP00000319210.8	Q9UNE2-2
	RPH3AL	ENST00000953554.1		c.715C>T	p.Arg239Trp	missense	Exon 7 of 9	ENSP00000623613.1

Frequencies

GnomAD3 genomes AF: 0.0000470 AC: 7 AN: 148930 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000496

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000200

Gnomad SAS AF: 0.000850

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000562 AC: 14 AN: 248940 AF XY: 0.0000519

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000899

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000336 AC: 49 AN: 1459958 Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25 AN XY: 726310

African (AFR) AF: 0.0000598 AC: 2 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39618

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53154

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5756

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1110736

Other (OTH) AF: 0.000116 AC: 7 AN: 60284

GnomAD4 genome AF: 0.0000470 AC: 7 AN: 149036 Hom.: 0 Cov.: 29 AF XY: 0.0000414 AC XY: 3 AN XY: 72410

African (AFR) AF: 0.0000495 AC: 2 AN: 40430

American (AMR) AF: 0.00 AC: 0 AN: 14634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.000200 AC: 1 AN: 4990

South Asian (SAS) AF: 0.000852 AC: 4 AN: 4696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67694

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.0000262 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.11
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.013
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.022	D
Polyphen		0.0	B
Vest4		0.14
MutPred		0.41		Loss of solvent accessibility (P = 0.0087)
MVP		0.32
MPC		0.061
ClinPred		0.058	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.043
gMVP		0.19
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.25		Position offset: -30

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

Other links and lift over

dbSNP: rs765780150; hg19: chr17-69444;