chr7-26346534-T-C

Variant names:

• chr7-26346534-T-C
• rs3801890
• NM_013322.3:c.24+68T>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.24+68T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,217,994 control chromosomes in the GnomAD database, including 88,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (16037 hom., cov: 32)
  • Exomes 𝑓: 0.35 (72372 hom.)
• Consequence: SNX10 NM_013322.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0470
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-26346534-T-C is Benign according to our data. Variant chr7-26346534-T-C is described in ClinVar as Benign. ClinVar VariationId is 1221420.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.637 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+68T>C		intron	N/A	NP_037454.2
	SNX10	NM_001318198.1		c.-20+68T>C		intron	N/A	NP_001305127.1	Q9Y5X0
	SNX10	NM_001362753.1		c.-148+68T>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.24+68T>C		intron	N/A	ENSP00000343709.5	Q9Y5X0-1
	SNX10	ENST00000396376.5	TSL:1	c.24+68T>C		intron	N/A	ENSP00000379661.1	Q9Y5X0-1
	SNX10	ENST00000446848.6	TSL:1	c.24+68T>C		intron	N/A	ENSP00000395474.3	Q9Y5X0-1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65913 AN: 151958 Hom.: 15987 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.353 AC: 376582 AN: 1065918 Hom.: 72372 AF XY: 0.363 AC XY: 199176 AN XY: 548818

African (AFR) AF: 0.648 AC: 16481 AN: 25450

American (AMR) AF: 0.436 AC: 19243 AN: 44180

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 11386 AN: 23622

East Asian (EAS) AF: 0.470 AC: 17753 AN: 37800

South Asian (SAS) AF: 0.599 AC: 46600 AN: 77800

European-Finnish (FIN) AF: 0.295 AC: 15663 AN: 53132

Middle Eastern (MID) AF: 0.569 AC: 2838 AN: 4988

European-Non Finnish (NFE) AF: 0.304 AC: 228257 AN: 751798

Other (OTH) AF: 0.389 AC: 18361 AN: 47148

GnomAD4 genome AF: 0.434 AC: 66028 AN: 152076 Hom.: 16037 Cov.: 32 AF XY: 0.437 AC XY: 32463 AN XY: 74364

African (AFR) AF: 0.643 AC: 26683 AN: 41482

American (AMR) AF: 0.403 AC: 6152 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1746 AN: 3472

East Asian (EAS) AF: 0.487 AC: 2516 AN: 5162

South Asian (SAS) AF: 0.609 AC: 2937 AN: 4820

European-Finnish (FIN) AF: 0.291 AC: 3081 AN: 10574

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21545 AN: 67970

Other (OTH) AF: 0.441 AC: 932 AN: 2114

Alfa AF: 0.370 Hom.: 8446

Bravo AF: 0.451

Asia WGS AF: 0.542 AC: 1883 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	-0.92
CADD	Benign	6.2
DANN	Benign	0.66
PhyloP100		-0.047
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: rs3801890; hg19: chr7-26386154; COSMIC: COSV58402171;