7-26362887-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013322.3(SNX10):​c.112-1648C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,988 control chromosomes in the GnomAD database, including 15,756 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 0.44 (15756 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

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>G		intron	N/A	NP_037454.2
	SNX10	NM_001318198.1		c.190-1648C>G		intron	N/A	NP_001305127.1
	SNX10	NM_001362753.1		c.190-1648C>G		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>G		intron	N/A	ENSP00000343709.5
	SNX10	ENST00000396376.5	TSL:1	c.112-1648C>G		intron	N/A	ENSP00000379661.1
	SNX10	ENST00000446848.6	TSL:1	c.112-1648C>G		intron	N/A	ENSP00000395474.3

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67477 AN: 151870 Hom.: 15740 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.444 AC: 67520 AN: 151988 Hom.: 15756 Cov.: 32 AF XY: 0.441 AC XY: 32784 AN XY: 74262

African (AFR) AF: 0.300 AC: 12413 AN: 41434

American (AMR) AF: 0.450 AC: 6878 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1746 AN: 3470

East Asian (EAS) AF: 0.461 AC: 2384 AN: 5166

South Asian (SAS) AF: 0.584 AC: 2814 AN: 4820

European-Finnish (FIN) AF: 0.443 AC: 4664 AN: 10530

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34977 AN: 67970

Other (OTH) AF: 0.479 AC: 1012 AN: 2112

Alfa AF: 0.310 Hom.: 812

Bravo AF: 0.437

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.81
DANN	Benign	0.27
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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;