Genetic Variant SNX10:c.312-8T>A (chr7-26371813-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_StrongBS1BS2

The NM_013322.3(SNX10):c.312-8T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,580,522 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 6 hom., cov: 33)

Exomes 𝑓: 0.011 ( 115 hom. )

Consequence

SNX10
NM_013322.3 splice_region, intron

Scores

Splicing: ADA: 0.0008578

Clinical Significance

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

Conservation

PhyloP100: -0.987

Publications

2 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 links:

SNX10-AS1 (HGNC:55845): (SNX10 antisense RNA 1)

SNX10-AS1 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=-0.89).

BP6

Variant 7-26371813-T-A is Benign according to our data. Variant chr7-26371813-T-A is described in ClinVar as Benign. ClinVar VariationId is 719907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00732 (1113/152144) while in subpopulation NFE AF = 0.0119 (807/67928). AF 95% confidence interval is 0.0112. There are 6 homozygotes in GnomAd4. There are 475 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

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.312-8T>A	splice_region intron	N/A	NP_037454.2
SNX10	NM_001318198.1		c.390-8T>A	splice_region intron	N/A	NP_001305127.1	Q9Y5X0
SNX10	NM_001362753.1		c.390-8T>A	splice_region 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.312-8T>A	splice_region intron	N/A	ENSP00000343709.5	Q9Y5X0-1
SNX10	ENST00000396376.5	TSL:1	c.312-8T>A	splice_region intron	N/A	ENSP00000379661.1	Q9Y5X0-1
SNX10	ENST00000446848.6	TSL:1	c.312-8T>A	splice_region intron	N/A	ENSP00000395474.3	Q9Y5X0-1

Frequencies

GnomAD3 genomes

AF:

0.00733

AC:

1114

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00544

Gnomad ASJ

AF:

0.00779

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00981

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00842

AC:

1979

AN:

234942

AF XY:

0.00822

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.00434

Gnomad ASJ exome

AF:

0.00737

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0130

Gnomad NFE exome

AF:

0.0129

Gnomad OTH exome

AF:

0.0110

GnomAD4 exome

AF:

0.0106

AC:

15183

AN:

1428378

Hom.:

115

Cov.:

AF XY:

0.0102

AC XY:

7284

AN XY:

711160

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

31972

American (AMR)

AF:

0.00439

AC:

178

AN:

40572

Ashkenazi Jewish (ASJ)

AF:

0.00660

AC:

167

AN:

25320

East Asian (EAS)

AF:

0.00

AC:

AN:

39498

South Asian (SAS)

AF:

0.000256

AC:

AN:

81994

European-Finnish (FIN)

AF:

0.0133

AC:

704

AN:

52822

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.0124

AC:

13523

AN:

1091508

Other (OTH)

AF:

0.00897

AC:

530

AN:

59070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

619

1238

1857

2476

3095

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.00732

AC:

1113

AN:

152144

Hom.:

Cov.:

AF XY:

0.00638

AC XY:

475

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

41534

American (AMR)

AF:

0.00543

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00779

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00981

AC:

104

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0119

AC:

807

AN:

67928

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

120

179

239

299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00906

Hom.:

Bravo

AF:

0.00733

EpiCase

AF:

0.0103

EpiControl

AF:

0.00949

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.029

(source)

DANN

Benign

0.35

PhyloP100

-0.99

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00086

dbscSNV1_RF

Benign

0.080

SpliceAI score (max)

0.090

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