Genetic Variant NM_013322.3:c.24+36T>A (chr7-26346502-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.195

Publications

6 publications found

Variant links:

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

SNX10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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

Gene	Transcript	Tags	HGVSc	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.355

AC XY:

239967

AN XY:

675328

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

14508

29016

43525

58033

72541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9878

19756

29634

39512

49390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.414

AC:

62948

AN:

152060

Hom.:

14163

Cov.:

AF XY:

0.417

AC XY:

31008

AN XY:

74340

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1836

3671

5507

7342

9178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive osteopetrosis 8 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.5

(source)

DANN

Benign

0.68

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over