Genetic Variant NM_152233.4:c.*159G>A (chr14-34562963-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152233.4(SNX6):c.*159G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 683,520 control chromosomes in the GnomAD database, including 35,600 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 6242 hom., cov: 33)

Exomes 𝑓: 0.32 ( 29358 hom. )

Consequence

SNX6
NM_152233.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.170

Publications

11 publications found

Variant links:

Genes affected

SNX6 (HGNC:14970): (sorting nexin 6) 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 associates with the long isoform of the leptin receptor, the transforming growth factor-beta family of receptor serine-threonine kinases, and with receptor tyrosine kinases for platelet-derived growth factor, insulin, and epidermal growth factor. This protein may form oligomeric complexes with family member proteins through interactions of both the PX domain and the coiled coil regions of the molecules. Translocation of this protein from the cytoplasm to the nucleus occurs after binding to proviral integration site 1 protein. This gene results in two transcripts encoding two distinct isoforms. [provided by RefSeq, Jul 2008]

SNX6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX6	NM_152233.4 link	c.*159G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000362031.10	NP_689419.3	Q9UNH7-1A0A0A0MRI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX6	ENST00000362031.10 link	c.*159G>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_152233.4	ENSP00000355217.5		Q9UNH7-1

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38658

AN:

152094

Hom.:

6241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0691

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.0943

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.301

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.265

GnomAD4 exome

AF:

0.320

AC:

170276

AN:

531308

Hom.:

29358

Cov.:

AF XY:

0.322

AC XY:

90142

AN XY:

280210

show subpopulations

African (AFR)

AF:

0.0659

AC:

912

AN:

13842

American (AMR)

AF:

0.189

AC:

4058

AN:

21432

Ashkenazi Jewish (ASJ)

AF:

0.305

AC:

4546

AN:

14918

East Asian (EAS)

AF:

0.111

AC:

3512

AN:

31566

South Asian (SAS)

AF:

0.273

AC:

13126

AN:

48142

European-Finnish (FIN)

AF:

0.309

AC:

13837

AN:

44840

Middle Eastern (MID)

AF:

0.304

AC:

686

AN:

2254

European-Non Finnish (NFE)

AF:

0.372

AC:

121087

AN:

325826

Other (OTH)

AF:

0.299

AC:

8512

AN:

28488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

5193

10385

15578

20770

25963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1084

2168

3252

4336

5420

<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:

0.254

AC:

38659

AN:

152212

Hom.:

6242

Cov.:

AF XY:

0.249

AC XY:

18536

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0690

AC:

2870

AN:

41566

American (AMR)

AF:

0.217

AC:

3309

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1087

AN:

3472

East Asian (EAS)

AF:

0.0941

AC:

488

AN:

5184

South Asian (SAS)

AF:

0.277

AC:

1335

AN:

4820

European-Finnish (FIN)

AF:

0.301

AC:

3186

AN:

10572

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.374

AC:

25407

AN:

68000

Other (OTH)

AF:

0.265

AC:

560

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1282

2565

3847

5130

6412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<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:

0.287

Hom.:

5305

Bravo

AF:

0.236

Asia WGS

AF:

0.195

AC:

680

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.0

(source)

DANN

Benign

0.71

PhyloP100

-0.17

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over