chr11-130880697-G-A

Variant names:

• chr11-130880697-G-A
• rs142783173
• NM_014758.3:c.2683C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_014758.3(SNX19):​c.2683C>T​(p.Arg895Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0071 in 1,612,362 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R895Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0071 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (94 hom.)
• Consequence: SNX19 NM_014758.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.55
• Publications: 9 publications found

Genes affected

SNX19 (HGNC:21532): (sorting nexin 19) Islet antigen-2 (IA-2) is an autoantigen in type 1 diabetes and plays a role in insulin secretion. IA-2 is found in dense-core secretory vesicles and interacts with the product of this gene, a sorting nexin. In mouse pancreatic beta-cells, the encoded protein influenced insulin secretion by stabilizing the number of dense-core secretory vesicles. [provided by RefSeq, Dec 2016]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009041548).
• BP6: Variant 11-130880697-G-A is Benign according to our data. Variant chr11-130880697-G-A is described in ClinVar as Benign. ClinVar VariationId is 784522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014758.3. 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
	SNX19	NM_014758.3	MANE Select	c.2683C>T	p.Arg895Trp	missense	Exon 9 of 11	NP_055573.3	Q92543-1
	SNX19	NM_001347918.2		c.2563C>T	p.Arg855Trp	missense	Exon 8 of 10	NP_001334847.2
	SNX19	NM_001347922.2		c.1012C>T	p.Arg338Trp	missense	Exon 10 of 12	NP_001334851.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX19	ENST00000265909.9	TSL:1 MANE Select	c.2683C>T	p.Arg895Trp	missense	Exon 9 of 11	ENSP00000265909.4	Q92543-1
	SNX19	ENST00000534726.5	TSL:1	c.403C>T	p.Arg135Trp	missense	Exon 5 of 7	ENSP00000433699.1	E9PJV7
	SNX19	ENST00000530330.1	TSL:1	n.419C>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.00707 AC: 1076 AN: 152182 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0485

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00667

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00859 AC: 2153 AN: 250582 AF XY: 0.00845

Gnomad AFR exome AF: 0.000985

Gnomad AMR exome AF: 0.00163

Gnomad ASJ exome AF: 0.00676

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0451

Gnomad NFE exome AF: 0.00858

Gnomad OTH exome AF: 0.00720

GnomAD4 exome AF: 0.00711 AC: 10375 AN: 1460062 Hom.: 94 Cov.: 30 AF XY: 0.00707 AC XY: 5131 AN XY: 726080

African (AFR) AF: 0.000747 AC: 25 AN: 33450

American (AMR) AF: 0.00197 AC: 88 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00820 AC: 214 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.000605 AC: 52 AN: 86018

European-Finnish (FIN) AF: 0.0417 AC: 2229 AN: 53400

Middle Eastern (MID) AF: 0.00417 AC: 24 AN: 5760

European-Non Finnish (NFE) AF: 0.00667 AC: 7406 AN: 1110646

Other (OTH) AF: 0.00559 AC: 337 AN: 60318

GnomAD4 genome AF: 0.00707 AC: 1076 AN: 152300 Hom.: 7 Cov.: 32 AF XY: 0.00873 AC XY: 650 AN XY: 74460

African (AFR) AF: 0.00120 AC: 50 AN: 41568

American (AMR) AF: 0.00183 AC: 28 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.0485 AC: 515 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00667 AC: 454 AN: 68024

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00571 Hom.: 4

Bravo AF: 0.00380

TwinsUK AF: 0.00728 AC: 27

ALSPAC AF: 0.00675 AC: 26

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00687 AC: 59

ExAC AF: 0.00865 AC: 1050

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00498

EpiControl AF: 0.00700

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.091
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.5
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.48
MVP		0.45
MPC		0.51
ClinPred		0.024	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.083
gMVP		0.31
Mutation Taster		=96/4	polymorphism

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: rs142783173; hg19: chr11-130750592;