7-26346502-T-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX10	NM_013322.3	c.24+36T>A		intron_variant		ENST00000338523.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX10	ENST00000338523.9	c.24+36T>A		intron_variant		1	NM_013322.3	P1

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

GnomAD3 exomes AF: 0.408 AC: 102504 AN: 251292 Hom.: 22529 AF XY: 0.413 AC XY: 56120 AN XY: 135836

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 SAS exome AF: 0.605

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

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.432

Gnomad4 ASJ exome AF: 0.482

Gnomad4 EAS exome AF: 0.471

Gnomad4 SAS exome AF: 0.599

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.384

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

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.430

Alfa AF: 0.393 Hom.: 2296

Bravo AF: 0.427

Asia WGS AF: 0.536 AC: 1859 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Autosomal recessive osteopetrosis 8 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.5
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs3801891; hg19: chr7-26386122; COSMIC: COSV58402166;