chr7-26346502-T-A

Variant names:

• chr7-26346502-T-A
• rs3801891
• NM_013322.3:c.24+36T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013322.3(SNX10):​c.24+36T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,496,684 control chromosomes in the GnomAD database, including 101,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14163 hom., cov: 32)
  • Exomes 𝑓: 0.35 (86926 hom.)
• Consequence: SNX10 NM_013322.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.195
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-26346502-T-A is Benign according to our data. Variant chr7-26346502-T-A is described in ClinVar as Benign. ClinVar VariationId is 1243137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.59 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.24+36T>A		intron	N/A	NP_037454.2
	SNX10	NM_001318198.1		c.-20+36T>A		intron	N/A	NP_001305127.1	Q9Y5X0
	SNX10	NM_001362753.1		c.-148+36T>A		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.24+36T>A		intron	N/A	ENSP00000343709.5	Q9Y5X0-1
	SNX10	ENST00000396376.5	TSL:1	c.24+36T>A		intron	N/A	ENSP00000379661.1	Q9Y5X0-1
	SNX10	ENST00000446848.6	TSL:1	c.24+36T>A		intron	N/A	ENSP00000395474.3	Q9Y5X0-1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62870 AN: 151942 Hom.: 14142 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.432

GnomAD2 exomes AF: 0.408 AC: 102504 AN: 251292 AF XY: 0.413

Gnomad AFR exome AF: 0.575

Gnomad AMR exome AF: 0.438

Gnomad ASJ exome AF: 0.487

Gnomad EAS exome AF: 0.487

Gnomad FIN exome AF: 0.293

Gnomad NFE exome AF: 0.325

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.346 AC: 465412 AN: 1344624 Hom.: 86926 Cov.: 22 AF XY: 0.355 AC XY: 239967 AN XY: 675328

African (AFR) AF: 0.575 AC: 17759 AN: 30878

American (AMR) AF: 0.432 AC: 19277 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 12219 AN: 25348

East Asian (EAS) AF: 0.471 AC: 18419 AN: 39114

South Asian (SAS) AF: 0.599 AC: 50042 AN: 83514

European-Finnish (FIN) AF: 0.296 AC: 15774 AN: 53362

Middle Eastern (MID) AF: 0.567 AC: 3135 AN: 5530

European-Non Finnish (NFE) AF: 0.305 AC: 307154 AN: 1005900

Other (OTH) AF: 0.384 AC: 21633 AN: 56404

GnomAD4 genome AF: 0.414 AC: 62948 AN: 152060 Hom.: 14163 Cov.: 32 AF XY: 0.417 AC XY: 31008 AN XY: 74340

African (AFR) AF: 0.570 AC: 23648 AN: 41480

American (AMR) AF: 0.400 AC: 6118 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1745 AN: 3468

East Asian (EAS) AF: 0.486 AC: 2515 AN: 5170

South Asian (SAS) AF: 0.609 AC: 2937 AN: 4826

European-Finnish (FIN) AF: 0.292 AC: 3083 AN: 10568

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21561 AN: 67952

Other (OTH) AF: 0.430 AC: 909 AN: 2114

Alfa AF: 0.393 Hom.: 2296

Bravo AF: 0.427

Asia WGS AF: 0.536 AC: 1859 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive osteopetrosis 8 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.68
PhyloP100		-0.20
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: rs3801891; hg19: chr7-26386122; COSMIC: COSV58402166;