rs533594428

Variant names:

• chr11-130906001-C-A
• rs533594428
• NM_014758.3:c.2395G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-130906001-C-A
• chr11-130906001-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_014758.3(SNX19):​c.2395G>T​(p.Val799Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNX19 NM_014758.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.918
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022891134).
• BP6: Variant 11-130906001-C-A is Benign according to our data. Variant chr11-130906001-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3167200.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2395G>T	p.Val799Leu	missense	Exon 7 of 11	NP_055573.3	Q92543-1
	SNX19	NM_001347918.2		c.2275G>T	p.Val759Leu	missense	Exon 6 of 10	NP_001334847.2
	SNX19	NM_001347919.2		c.2395G>T	p.Val799Leu	missense	Exon 7 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.2395G>T	p.Val799Leu	missense	Exon 7 of 11	ENSP00000265909.4	Q92543-1
	SNX19	ENST00000533214.1	TSL:1	c.2344G>T	p.Val782Leu	missense	Exon 7 of 8	ENSP00000435390.1	Q92543-2
	SNX19	ENST00000534726.5	TSL:1	c.115G>T	p.Val39Leu	missense	Exon 3 of 7	ENSP00000433699.1	E9PJV7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.063
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.020
DANN	Benign	0.23
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-0.92
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.022
Sift	Benign	0.78	T
Sift4G	Benign	0.86	T
Polyphen		0.0	B
Vest4		0.080
MutPred		0.18		Gain of loop (P = 0.0045)
MVP		0.076
MPC		0.11
ClinPred		0.026	T
GERP RS		-7.0
Varity_R		0.077
gMVP		0.095
Mutation Taster		=99/1	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: rs533594428; hg19: chr11-130775896;