chr11-130903346-G-C

Variant names:

• chr11-130903346-G-C
• rs144457394
• NM_014758.3:c.2482C>G

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.2482C>G​(p.Leu828Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,613,236 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (21 hom.)
• Consequence: SNX19 NM_014758.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.60
• Publications: 5 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=0.009277552).
• BP6: Variant 11-130903346-G-C is Benign according to our data. Variant chr11-130903346-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 788365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 21 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.2482C>G	p.Leu828Val	missense	Exon 8 of 11	NP_055573.3	Q92543-1
	SNX19	NM_001347918.2		c.2362C>G	p.Leu788Val	missense	Exon 7 of 10	NP_001334847.2
	SNX19	NM_001347919.2		c.2482C>G	p.Leu828Val	missense	Exon 8 of 10	NP_001334848.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX19	ENST00000265909.9	TSL:1 MANE Select	c.2482C>G	p.Leu828Val	missense	Exon 8 of 11	ENSP00000265909.4	Q92543-1
	SNX19	ENST00000534726.5	TSL:1	c.202C>G	p.Leu68Val	missense	Exon 4 of 7	ENSP00000433699.1	E9PJV7
	SNX19	ENST00000528555.5	TSL:2	c.622C>G	p.Leu208Val	missense	Exon 8 of 11	ENSP00000435122.1	E9PLV3

Frequencies

GnomAD3 genomes AF: 0.00283 AC: 430 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00497

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00278 AC: 698 AN: 251260 AF XY: 0.00273

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00232

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000878

Gnomad NFE exome AF: 0.00466

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00469 AC: 6845 AN: 1460950 Hom.: 21 Cov.: 31 AF XY: 0.00451 AC XY: 3281 AN XY: 726818

African (AFR) AF: 0.000807 AC: 27 AN: 33452

American (AMR) AF: 0.00275 AC: 123 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000650 AC: 56 AN: 86210

European-Finnish (FIN) AF: 0.00152 AC: 81 AN: 53416

Middle Eastern (MID) AF: 0.00155 AC: 8 AN: 5162

European-Non Finnish (NFE) AF: 0.00569 AC: 6321 AN: 1111862

Other (OTH) AF: 0.00365 AC: 220 AN: 60310

GnomAD4 genome AF: 0.00282 AC: 430 AN: 152286 Hom.: 0 Cov.: 32 AF XY: 0.00247 AC XY: 184 AN XY: 74464

African (AFR) AF: 0.00111 AC: 46 AN: 41556

American (AMR) AF: 0.00176 AC: 27 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00497 AC: 338 AN: 68026

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00409 Hom.: 1

Bravo AF: 0.00303

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00431 AC: 37

ExAC AF: 0.00289 AC: 351

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00529

EpiControl AF: 0.00533

ClinVar

ClinVar submissions

Significance: Likely 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	0.093
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.0093	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.6
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.063
Sift	Benign	0.035	D
Sift4G	Benign	0.071	T
Polyphen		0.052	B
Vest4		0.28
MVP		0.68
MPC		0.12
ClinPred		0.013	T
GERP RS		2.6
Varity_R		0.042
gMVP		0.38
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs144457394; hg19: chr11-130773241;