11-130903355-G-A

Variant names:

• chr11-130903355-G-A
• rs1945398077
• NM_014758.3:c.2473C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_014758.3(SNX19):​c.2473C>T​(p.Leu825Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX19 NM_014758.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP7: Synonymous conserved (PhyloP=1.82 with no splicing effect.

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.2473C>T	p.Leu825Leu	synonymous	Exon 8 of 11	NP_055573.3	Q92543-1
	SNX19	NM_001347918.2		c.2353C>T	p.Leu785Leu	synonymous	Exon 7 of 10	NP_001334847.2
	SNX19	NM_001347919.2		c.2473C>T	p.Leu825Leu	synonymous	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.2473C>T	p.Leu825Leu	synonymous	Exon 8 of 11	ENSP00000265909.4	Q92543-1
	SNX19	ENST00000534726.5	TSL:1	c.193C>T	p.Leu65Leu	synonymous	Exon 4 of 7	ENSP00000433699.1	E9PJV7
	SNX19	ENST00000528555.5	TSL:2	c.613C>T	p.Leu205Leu	synonymous	Exon 8 of 11	ENSP00000435122.1	E9PLV3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	7.4
DANN	Benign	0.75
PhyloP100		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1945398077; hg19: chr11-130773250;