NM_013322.3:c.-23-331T>C

Variant names:

• chr7-26346089-T-C
• rs12537548
• NM_013322.3:c.-23-331T>C

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.-23-331T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 152,232 control chromosomes in the GnomAD database, including 523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.076 (523 hom., cov: 32)
• Consequence: SNX10 NM_013322.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.433
• Publications: 0 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 7-26346089-T-C is Benign according to our data. Variant chr7-26346089-T-C is described in ClinVar as Benign. ClinVar VariationId is 1227601.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.105 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.-23-331T>C		intron	N/A	NP_037454.2
	SNX10	NM_001318198.1		c.-66-331T>C		intron	N/A	NP_001305127.1	Q9Y5X0
	SNX10	NM_001362753.1		c.-194-331T>C		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.-23-331T>C		intron	N/A	ENSP00000343709.5	Q9Y5X0-1
	SNX10	ENST00000396376.5	TSL:1	c.-23-331T>C		intron	N/A	ENSP00000379661.1	Q9Y5X0-1
	SNX10	ENST00000446848.6	TSL:1	c.-23-331T>C		intron	N/A	ENSP00000395474.3	Q9Y5X0-1

Frequencies

GnomAD3 genomes AF: 0.0758 AC: 11528 AN: 152116 Hom.: 521 Cov.: 32

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.0991

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0676

Gnomad SAS AF: 0.0981

Gnomad FIN AF: 0.0996

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.0727

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

GnomAD4 genome AF: 0.0758 AC: 11535 AN: 152232 Hom.: 523 Cov.: 32 AF XY: 0.0786 AC XY: 5853 AN XY: 74434

African (AFR) AF: 0.0344 AC: 1431 AN: 41554

American (AMR) AF: 0.110 AC: 1674 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 401 AN: 3472

East Asian (EAS) AF: 0.0678 AC: 351 AN: 5178

South Asian (SAS) AF: 0.0989 AC: 477 AN: 4824

European-Finnish (FIN) AF: 0.0996 AC: 1056 AN: 10602

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0866 AC: 5888 AN: 68006

Other (OTH) AF: 0.0715 AC: 151 AN: 2112

Alfa AF: 0.0853 Hom.: 87

Bravo AF: 0.0733

Asia WGS AF: 0.0750 AC: 261 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	4.1
DANN	Benign	0.38
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12537548; hg19: chr7-26385709;