Genetic Variant NM_001330723.2:c.16G>A (chr1-151612217-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001330723.2(SNX27):c.16G>A(p.Gly6Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000166 in 1,206,912 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G6V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

SNX27
NM_001330723.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.38

Publications

1 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 links:

ENSG00000250734 (HGNC:):

ENSG00000250734 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.16G>A	p.Gly6Arg	missense	Exon 1 of 12	NP_001317652.1	Q96L92-1
SNX27	NM_030918.6		c.16G>A	p.Gly6Arg	missense	Exon 1 of 12	NP_112180.4
SNX27	NM_001437601.1		c.16G>A	p.Gly6Arg	missense	Exon 1 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.16G>A	p.Gly6Arg	missense	Exon 1 of 12	ENSP00000400333.2	Q96L92-1
SNX27	ENST00000368843.8	TSL:1	c.16G>A	p.Gly6Arg	missense	Exon 1 of 12	ENSP00000357836.3	Q96L92-3
SNX27	ENST00000368841.7	TSL:1	n.16G>A		non_coding_transcript_exon	Exon 1 of 12	ENSP00000357834.2	H7C603

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000166

AC:

AN:

1206912

Hom.:

Cov.:

AF XY:

0.00000171

AC XY:

AN XY:

583934

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24288

American (AMR)

AF:

0.00

AC:

AN:

11154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16856

East Asian (EAS)

AF:

0.00

AC:

AN:

27056

South Asian (SAS)

AF:

0.00

AC:

AN:

53352

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4472

European-Non Finnish (NFE)

AF:

0.00000203

AC:

AN:

984934

Other (OTH)

AF:

0.00

AC:

AN:

49260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.74

M_CAP

Pathogenic

0.95

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

6.4

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.81

REVEL

Benign

0.27

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.010

Polyphen

0.99

Vest4

0.55

MutPred

0.42

Gain of helix (P = 0.0496)

MVP

0.59

MPC

1.7

ClinPred

0.82

GERP RS

3.1

PromoterAI

-0.029

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.68

Mutation Taster

=72/28

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over