11-130903262-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014758.3(SNX19):​c.2566G>C​(p.Val856Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V856I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX19 NM_014758.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14430189).

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.2566G>C	p.Val856Leu	missense	Exon 8 of 11	NP_055573.3	Q92543-1
	SNX19	NM_001347918.2		c.2446G>C	p.Val816Leu	missense	Exon 7 of 10	NP_001334847.2
	SNX19	NM_001347919.2		c.2566G>C	p.Val856Leu	missense	Exon 8 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.2566G>C	p.Val856Leu	missense	Exon 8 of 11	ENSP00000265909.4	Q92543-1
	SNX19	ENST00000534726.5	TSL:1	c.286G>C	p.Val96Leu	missense	Exon 4 of 7	ENSP00000433699.1	E9PJV7
	SNX19	ENST00000528555.5	TSL:2	c.706G>C	p.Val236Leu	missense	Exon 8 of 11	ENSP00000435122.1	E9PLV3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.7
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.049
Sift	Benign	0.16	T
Sift4G	Benign	0.25	T
Polyphen		0.0090	B
Vest4		0.33
MVP		0.22
MPC		0.13
ClinPred		0.37	T
GERP RS		3.7
Varity_R		0.094
gMVP		0.36
Mutation Taster		=94/6	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: rs138056272; hg19: chr11-130773157;