dbSNP rs61762678: SNX27:p.Val323Met (chr1-151665993-G-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_001330723.2(SNX27):c.967G>A(p.Val323Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,611,398 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 15 hom. )

Consequence

SNX27
NM_001330723.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 9.07

Publications

7 publications found

Variant links:

Genes affected

SNX27 (HGNC:20073): (sorting nexin 27) This gene encodes a member of the sorting nexin family, a diverse group of cytoplasmic and membrane-associated proteins involved in endocytosis of plasma membrane receptors and protein trafficking through these compartments. All members of this protein family contain a phosphoinositide binding domain (PX domain). A highly similar protein in mouse is responsible for the specific recruitment of an isoform of serotonin 5-hydroxytryptamine 4 receptor into early endosomes, suggesting the analogous role for the human protein. [provided by RefSeq, Jul 2008]

SNX27 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

SNX27 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 (MetaRNN=0.010459214).

BP6

Variant 1-151665993-G-A is Benign according to our data. Variant chr1-151665993-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 462820.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 = 0.0029 (442/152330) while in subpopulation NFE AF = 0.00435 (296/68030). AF 95% confidence interval is 0.00394. There are 2 homozygotes in GnomAd4. There are 241 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 442 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330723.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX27	NM_001330723.2	MANE Select	c.967G>A	p.Val323Met	missense	Exon 6 of 12	NP_001317652.1	Q96L92-1
SNX27	NM_030918.6		c.967G>A	p.Val323Met	missense	Exon 6 of 12	NP_112180.4
SNX27	NM_001437601.1		c.664G>A	p.Val222Met	missense	Exon 5 of 11	NP_001424530.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX27	ENST00000458013.7	TSL:5 MANE Select	c.967G>A	p.Val323Met	missense	Exon 6 of 12	ENSP00000400333.2	Q96L92-1
SNX27	ENST00000368843.8	TSL:1	c.967G>A	p.Val323Met	missense	Exon 6 of 12	ENSP00000357836.3	Q96L92-3
SNX27	ENST00000368838.2	TSL:1	c.562G>A	p.Val188Met	missense	Exon 5 of 10	ENSP00000357831.2	A0A5H1ZRP6

Frequencies

GnomAD3 genomes

AF:

0.00290

AC:

442

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00932

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00435

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00316

AC:

790

AN:

249942

AF XY:

0.00319

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.000236

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00759

Gnomad NFE exome

AF:

0.00509

Gnomad OTH exome

AF:

0.00347

GnomAD4 exome

AF:

0.00334

AC:

4879

AN:

1459068

Hom.:

Cov.:

AF XY:

0.00326

AC XY:

2365

AN XY:

725828

show subpopulations

African (AFR)

AF:

0.000629

AC:

AN:

33408

American (AMR)

AF:

0.000292

AC:

AN:

44536

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39616

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85848

European-Finnish (FIN)

AF:

0.00802

AC:

428

AN:

53334

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00383

AC:

4253

AN:

1110222

Other (OTH)

AF:

0.00264

AC:

159

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

214

428

642

856

1070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

288

432

576

720

<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:

0.00290

AC:

442

AN:

152330

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

241

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.000842

AC:

AN:

41574

American (AMR)

AF:

0.000392

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00932

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00435

AC:

296

AN:

68030

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

105

131

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:

0.00350

Hom.:

Bravo

AF:

0.00203

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00363

AC:

441

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Severe myoclonic epilepsy in infancy (1)

SNX27-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.081

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.011

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.0

PhyloP100

9.1

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.88

REVEL

Uncertain

0.42

Sift

Benign

0.35

Sift4G

Benign

0.49

Polyphen

0.20

Vest4

0.86

MVP

0.85

MPC

0.68

ClinPred

0.021

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.099

gMVP

0.61

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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