chr7-26309593-G-T

Variant names:

• chr7-26309593-G-T
• rs4563785
• NM_013322.3:c.-24+17507G>T

Variant summary

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

The NM_013322.3(SNX10):​c.-24+17507G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 152,204 control chromosomes in the GnomAD database, including 411 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 0.062 (411 hom., cov: 32)
• Consequence: SNX10 NM_013322.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• 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: 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0886 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.-24+17507G>T		intron	N/A	NP_037454.2
	SNX10	NM_001318198.1		c.-67+17507G>T		intron	N/A	NP_001305127.1
	SNX10	NM_001362753.1		c.-195+17507G>T		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.-24+17507G>T		intron	N/A	ENSP00000343709.5
	SNX10	ENST00000396376.5	TSL:1	c.-24+16435G>T		intron	N/A	ENSP00000379661.1
	SNX10	ENST00000446848.6	TSL:1	c.-24+17460G>T		intron	N/A	ENSP00000395474.3

Frequencies

GnomAD3 genomes AF: 0.0622 AC: 9454 AN: 152086 Hom.: 410 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0404

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0898

Gnomad FIN AF: 0.0876

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0905

Gnomad OTH AF: 0.0607

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

GnomAD4 genome AF: 0.0621 AC: 9452 AN: 152204 Hom.: 411 Cov.: 32 AF XY: 0.0629 AC XY: 4680 AN XY: 74408

African (AFR) AF: 0.0160 AC: 664 AN: 41522

American (AMR) AF: 0.0403 AC: 616 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5184

South Asian (SAS) AF: 0.0905 AC: 437 AN: 4828

European-Finnish (FIN) AF: 0.0876 AC: 927 AN: 10580

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0905 AC: 6153 AN: 68002

Other (OTH) AF: 0.0596 AC: 126 AN: 2114

Alfa AF: 0.0673 Hom.: 271

Bravo AF: 0.0547

Asia WGS AF: 0.0400 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.69
DANN	Benign	0.64
PhyloP100		-0.32
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: rs4563785; hg19: chr7-26349213;