rs144457394

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-130903346-G-A
• chr11-130903346-G-C

Variant summary

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

The NM_014758.3(SNX19):​c.2482C>T​(p.Leu828Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,460,962 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 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: 0.000011 (0 hom.)
• Consequence: SNX19 NM_014758.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX19	NM_014758.3	c.2482C>T	p.Leu828Phe	missense_variant	Exon 8 of 11	ENST00000265909.9	NP_055573.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX19	ENST00000265909.9	c.2482C>T	p.Leu828Phe	missense_variant	Exon 8 of 11	1	NM_014758.3	ENSP00000265909.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1460962 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 726822

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: 0.0000144

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	0.17
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0052	T;.;.;.
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D;D;.;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.69	N;.;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.96	N;N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.076	T;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D
Polyphen		0.96	D;.;.;.
Vest4		0.41
MutPred		0.61		Loss of stability (P = 0.0325);.;.;.;
MVP		0.80
MPC		0.47
ClinPred		0.69	D
GERP RS		2.6
Varity_R		0.032
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-130773241;