11-130906716-C-G

Variant names:

• chr11-130906716-C-G
• NM_014758.3:c.2171G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014758.3(SNX19):​c.2171G>C​(p.Arg724Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNX19 NM_014758.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.88
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35018784).

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.2171G>C	p.Arg724Thr	missense	Exon 6 of 11	NP_055573.3	Q92543-1
	SNX19	NM_001347918.2		c.2051G>C	p.Arg684Thr	missense	Exon 5 of 10	NP_001334847.2
	SNX19	NM_001347919.2		c.2171G>C	p.Arg724Thr	missense	Exon 6 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.2171G>C	p.Arg724Thr	missense	Exon 6 of 11	ENSP00000265909.4	Q92543-1
	SNX19	ENST00000533214.1	TSL:1	c.2171G>C	p.Arg724Thr	missense	Exon 6 of 8	ENSP00000435390.1	Q92543-2
	SNX19	ENST00000534726.5	TSL:1	c.-110G>C		5_prime_UTR	Exon 2 of 7	ENSP00000433699.1	E9PJV7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Polyphen		0.96	D
Vest4		0.47
MutPred		0.31		Gain of phosphorylation at R724 (P = 0.0225)
MVP		0.72
MPC		0.58
ClinPred		0.90	D
GERP RS		3.8
Varity_R		0.18
gMVP		0.58
Mutation Taster		=59/41	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

hg19: chr11-130776611;