7-26346206-T-G

Variant names:

• chr7-26346206-T-G
• rs10951130
• NM_013322.3:c.-23-214T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013322.3(SNX10):​c.-23-214T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,020 control chromosomes in the GnomAD database, including 3,630 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3630 hom., cov: 31)
• Consequence: SNX10 NM_013322.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.251
• Publications: 4 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: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, PanelApp Australia
• autosomal recessive osteopetrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-26346206-T-G is Benign according to our data. Variant chr7-26346206-T-G is described in ClinVar as Benign. ClinVar VariationId is 1286408.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX10	NM_013322.3	MANE Select	c.-23-214T>G		intron	N/A	NP_037454.2
	SNX10	NM_001318198.1		c.-66-214T>G		intron	N/A	NP_001305127.1	Q9Y5X0
	SNX10	NM_001362753.1		c.-194-214T>G		intron	N/A	NP_001349682.1	B4DJM0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX10	ENST00000338523.9	TSL:1 MANE Select	c.-23-214T>G		intron	N/A	ENSP00000343709.5	Q9Y5X0-1
	SNX10	ENST00000396376.5	TSL:1	c.-23-214T>G		intron	N/A	ENSP00000379661.1	Q9Y5X0-1
	SNX10	ENST00000446848.6	TSL:1	c.-23-214T>G		intron	N/A	ENSP00000395474.3	Q9Y5X0-1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30925 AN: 151902 Hom.: 3618 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.204 AC: 30961 AN: 152020 Hom.: 3630 Cov.: 31 AF XY: 0.208 AC XY: 15429 AN XY: 74304

African (AFR) AF: 0.256 AC: 10615 AN: 41434

American (AMR) AF: 0.237 AC: 3624 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3468

East Asian (EAS) AF: 0.449 AC: 2311 AN: 5144

South Asian (SAS) AF: 0.194 AC: 933 AN: 4818

European-Finnish (FIN) AF: 0.203 AC: 2144 AN: 10586

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9970 AN: 67986

Other (OTH) AF: 0.193 AC: 408 AN: 2110

Alfa AF: 0.130 Hom.: 314

Bravo AF: 0.213

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.89
DANN	Benign	0.49
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10951130; hg19: chr7-26385826; COSMIC: COSV58401334;