rs199592034

Variant names:

• chr11-130879634-G-A
• rs199592034
• NM_014758.3:c.2836C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-130879634-G-A
• chr11-130879634-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014758.3(SNX19):​c.2836C>T​(p.Leu946Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SNX19 NM_014758.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.892

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23480988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX19	NM_014758.3	c.2836C>T	p.Leu946Phe	missense_variant	Exon 10 of 11	ENST00000265909.9	NP_055573.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX19	ENST00000265909.9	c.2836C>T	p.Leu946Phe	missense_variant	Exon 10 of 11	1	NM_014758.3	ENSP00000265909.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251092 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135694

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461602 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0039	T;.;.;.;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.86	D;D;D;.;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.23	T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.82	N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.71	T;T;T;T;T
Sift4G	Benign	0.72	T;T;T;T;T
Polyphen		0.93	P;.;.;.;.
Vest4		0.50
MutPred		0.66		Loss of helix (P = 0.2022);.;.;.;.;
MVP		0.26
MPC		0.17
ClinPred		0.31	T
GERP RS		3.2
Varity_R		0.10
gMVP		0.15

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

Publications

LitVar

Other links and lift over

dbSNP: rs199592034; hg19: chr11-130749529;