Genetic Variant SNX13:c.1954-11_1954-9dupTTT (chr7-17814950-AAG-AAGAAA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_015132.5(SNX13):c.1954-11_1954-9dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0020 ( 3 hom., cov: 0)

Exomes 𝑓: 0.043 ( 52 hom. )

Consequence

SNX13
NM_015132.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

Publications

2 publications found

Variant links:

Genes affected

SNX13 (HGNC:21335): (sorting nexin 13) This gene encodes a PHOX domain- and RGS domain-containing protein that belongs to the sorting nexin (SNX) family and the regulator of G protein signaling (RGS) family. The PHOX domain is a phosphoinositide binding domain, and the SNX family members are involved in intracellular trafficking. The RGS family members are regulatory molecules that act as GTPase activating proteins for G alpha subunits of heterotrimeric G proteins. The RGS domain of this protein interacts with G alpha(s), accelerates its GTP hydrolysis, and attenuates G alpha(s)-mediated signaling. Overexpression of this protein delayes lysosomal degradation of the epidermal growth factor receptor. Because of its bifunctional role, this protein may link heterotrimeric G protein signaling and vesicular trafficking. [provided by RefSeq, Jul 2008]

SNX13 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 267 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015132.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNX13	NM_015132.5	MANE Select	c.1954-11_1954-9dupTTT	intron	N/A	NP_055947.1	Q9Y5W8-2
SNX13	NM_001350862.2		c.1987-11_1987-9dupTTT	intron	N/A	NP_001337791.1	Q9Y5W8-1
SNX13	NM_001350863.2		c.1714-11_1714-9dupTTT	intron	N/A	NP_001337792.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNX13	ENST00000428135.7	TSL:1 MANE Select	c.1954-9_1954-8insTTT	intron	N/A	ENSP00000398789.2	Q9Y5W8-2
SNX13	ENST00000611725.4	TSL:1	c.1987-9_1987-8insTTT	intron	N/A	ENSP00000479044.1	A0A087WUZ7
SNX13	ENST00000496855.1	TSL:1	n.298-9_298-8insTTT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00205

AC:

267

AN:

130340

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00101

Gnomad ASJ

AF:

0.000949

Gnomad EAS

AF:

0.00107

Gnomad SAS

AF:

0.00300

Gnomad FIN

AF:

0.000487

Gnomad MID

AF:

0.00365

Gnomad NFE

AF:

0.000854

Gnomad OTH

AF:

0.000563

GnomAD2 exomes

AF:

0.0360

AC:

1227

AN:

34130

AF XY:

0.0381

show subpopulations

Gnomad AFR exome

AF:

0.0544

Gnomad AMR exome

AF:

0.0290

Gnomad ASJ exome

AF:

0.0322

Gnomad EAS exome

AF:

0.0498

Gnomad FIN exome

AF:

0.0233

Gnomad NFE exome

AF:

0.0360

Gnomad OTH exome

AF:

0.0359

GnomAD4 exome

AF:

0.0429

AC:

46037

AN:

1072292

Hom.:

Cov.:

AF XY:

0.0435

AC XY:

22656

AN XY:

521270

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0847

AC:

1722

AN:

20328

American (AMR)

AF:

0.0426

AC:

407

AN:

9546

Ashkenazi Jewish (ASJ)

AF:

0.0464

AC:

784

AN:

16880

East Asian (EAS)

AF:

0.0670

AC:

1629

AN:

24308

South Asian (SAS)

AF:

0.0694

AC:

2773

AN:

39958

European-Finnish (FIN)

AF:

0.0282

AC:

865

AN:

30670

Middle Eastern (MID)

AF:

0.0427

AC:

177

AN:

4150

European-Non Finnish (NFE)

AF:

0.0403

AC:

35561

AN:

882636

Other (OTH)

AF:

0.0484

AC:

2119

AN:

43816

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.298

Heterozygous variant carriers

3389

6779

10168

13558

16947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1480

2960

4440

5920

7400

<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:

0.00205

AC:

267

AN:

130354

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

139

AN XY:

62478

show subpopulations

African (AFR)

AF:

0.00484

AC:

177

AN:

36582

American (AMR)

AF:

0.00101

AC:

AN:

12916

Ashkenazi Jewish (ASJ)

AF:

0.000949

AC:

AN:

3160

East Asian (EAS)

AF:

0.00107

AC:

AN:

4674

South Asian (SAS)

AF:

0.00302

AC:

AN:

4300

European-Finnish (FIN)

AF:

0.000487

AC:

AN:

6160

Middle Eastern (MID)

AF:

0.00394

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.000854

AC:

AN:

59738

Other (OTH)

AF:

0.000559

AC:

AN:

1790

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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chr7-17814952-G-GAAAAA

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