NM_013322.3:c.-23-333C>T

Variant names:

• chr7-26346087-C-T
• rs12534819
• NM_013322.3:c.-23-333C>T

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.-23-333C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,172 control chromosomes in the GnomAD database, including 1,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1232 hom., cov: 31)
• Consequence: SNX10 NM_013322.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.171
• Publications: 1 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=-0.88).
• BP6: Variant 7-26346087-C-T is Benign according to our data. Variant chr7-26346087-C-T is described in ClinVar as Benign. ClinVar VariationId is 1239347.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 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.-23-333C>T		intron	N/A	NP_037454.2
	SNX10	NM_001318198.1		c.-66-333C>T		intron	N/A	NP_001305127.1	Q9Y5X0
	SNX10	NM_001362753.1		c.-194-333C>T		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.-23-333C>T		intron	N/A	ENSP00000343709.5	Q9Y5X0-1
	SNX10	ENST00000396376.5	TSL:1	c.-23-333C>T		intron	N/A	ENSP00000379661.1	Q9Y5X0-1
	SNX10	ENST00000446848.6	TSL:1	c.-23-333C>T		intron	N/A	ENSP00000395474.3	Q9Y5X0-1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18910 AN: 152054 Hom.: 1232 Cov.: 31

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.124 AC: 18925 AN: 152172 Hom.: 1232 Cov.: 31 AF XY: 0.125 AC XY: 9301 AN XY: 74410

African (AFR) AF: 0.111 AC: 4593 AN: 41512

American (AMR) AF: 0.148 AC: 2268 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3472

East Asian (EAS) AF: 0.176 AC: 908 AN: 5170

South Asian (SAS) AF: 0.118 AC: 570 AN: 4824

European-Finnish (FIN) AF: 0.113 AC: 1195 AN: 10596

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8457 AN: 67998

Other (OTH) AF: 0.118 AC: 249 AN: 2108

Alfa AF: 0.124 Hom.: 417

Bravo AF: 0.128

Asia WGS AF: 0.158 AC: 549 AN: 3478

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	-0.88
CADD	Benign	0.43
DANN	Benign	0.61
PhyloP100		-0.17
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: rs12534819; hg19: chr7-26385707; COSMIC: COSV58402563;