rs138056272

Variant names:

• chr11-130903262-C-A
• rs138056272
• NM_014758.3:c.2566G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-130903262-C-A
• chr11-130903262-C-G
• chr11-130903262-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014758.3(SNX19):​c.2566G>T​(p.Val856Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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: 6.8e-7 (0 hom.)
• Consequence: SNX19 NM_014758.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.839

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX19	NM_014758.3	c.2566G>T	p.Val856Phe	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.2566G>T	p.Val856Phe	missense_variant	Exon 8 of 11	1	NM_014758.3	ENSP00000265909.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461404 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727022

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T;.;.;.
Eigen	Benign	-0.091
Eigen_PC	Benign	-0.0090
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.94	D;D;.;D
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.84	D;D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L;.;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.84	P;.;.;.
Vest4		0.72
MutPred		0.74		Loss of MoRF binding (P = 0.101);.;.;.;
MVP		0.40
MPC		0.45
ClinPred		0.91	D
GERP RS		3.7
Varity_R		0.49
gMVP		0.76

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: rs138056272; hg19: chr11-130773157;