rs2699808

Variant names:

• chr7-26362887-C-A
• rs2699808
• NM_013322.3:c.112-1648C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-26362887-C-A
• chr7-26362887-C-G
• chr7-26362887-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_013322.3(SNX10):​c.112-1648C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 152,042 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.0012 (2 hom., cov: 32)
• Consequence: SNX10 NM_013322.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620
• Publications: 2 publications found

Genes affected

SNX10 (HGNC:14974): (sorting nexin 10) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein does not contain a coiled coil region, like some family members. This gene may play a role in regulating endosome homeostasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

SNX10 Gene-Disease associations (from GenCC):

• autosomal recessive osteopetrosis 8

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• autosomal recessive osteopetrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00123 (187/152042) while in subpopulation NFE AF = 0.00163 (111/67978). AF 95% confidence interval is 0.00139. There are 2 homozygotes in GnomAd4. There are 89 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013322.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX10	NM_013322.3	MANE Select	c.112-1648C>A		intron	N/A	NP_037454.2
	SNX10	NM_001318198.1		c.190-1648C>A		intron	N/A	NP_001305127.1
	SNX10	NM_001362753.1		c.190-1648C>A		intron	N/A	NP_001349682.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX10	ENST00000338523.9	TSL:1 MANE Select	c.112-1648C>A		intron	N/A	ENSP00000343709.5
	SNX10	ENST00000396376.5	TSL:1	c.112-1648C>A		intron	N/A	ENSP00000379661.1
	SNX10	ENST00000446848.6	TSL:1	c.112-1648C>A		intron	N/A	ENSP00000395474.3

Frequencies

GnomAD3 genomes AF: 0.00117 AC: 178 AN: 151924 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.000478

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00123 AC: 187 AN: 152042 Hom.: 2 Cov.: 32 AF XY: 0.00120 AC XY: 89 AN XY: 74300

African (AFR) AF: 0.00147 AC: 61 AN: 41454

American (AMR) AF: 0.000916 AC: 14 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00163 AC: 111 AN: 67978

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000287 Hom.: 812

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.73
DANN	Benign	0.12
PhyloP100		-0.62
Mutation Taster		=100/0	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: rs2699808; hg19: chr7-26402507;