Genetic Variant SNX21:p.Ala11Thr (chr20-45834210-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033421.4(SNX21):c.31G>A(p.Ala11Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000946 in 1,373,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A11S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000095 ( 0 hom. )

Consequence

SNX21
NM_033421.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.43

Publications

0 publications found

Variant links:

Genes affected

SNX21 (HGNC:16154): (sorting nexin family member 21) 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. The specific function of this protein has not been determined. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

SNX21 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22813702).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033421.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX21	NM_033421.4	MANE Select	c.31G>A	p.Ala11Thr	missense	Exon 2 of 4	NP_219489.1	Q969T3-1
SNX21	NM_152897.3		c.31G>A	p.Ala11Thr	missense	Exon 2 of 5	NP_690857.1	Q969T3-2
SNX21	NM_001042633.3		c.31G>A	p.Ala11Thr	missense	Exon 2 of 5	NP_001036098.1	A0A0S2Z632

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX21	ENST00000491381.6	TSL:1 MANE Select	c.31G>A	p.Ala11Thr	missense	Exon 2 of 4	ENSP00000418593.1	Q969T3-1
SNX21	ENST00000342644.9	TSL:1	c.31G>A	p.Ala11Thr	missense	Exon 2 of 5	ENSP00000344586.5	Q969T3-2
SNX21	ENST00000462307.5	TSL:1	c.31G>A	p.Ala11Thr	missense	Exon 2 of 5	ENSP00000420169.1	Q969T3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000946

AC:

AN:

1373504

Hom.:

Cov.:

AF XY:

0.00000886

AC XY:

AN XY:

677020

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31162

American (AMR)

AF:

0.00

AC:

AN:

33220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21524

East Asian (EAS)

AF:

0.00

AC:

AN:

38218

South Asian (SAS)

AF:

0.00

AC:

AN:

74482

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4976

European-Non Finnish (NFE)

AF:

0.0000111

AC:

AN:

1078206

Other (OTH)

AF:

0.0000176

AC:

AN:

56804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.033

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.9

PhyloP100

2.4

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.040

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0

Polyphen

0.087

Vest4

0.34

MutPred

0.25

Gain of phosphorylation at A11 (P = 0.0519)

MVP

0.36

MPC

0.24

ClinPred

0.96

GERP RS

3.9

PromoterAI

-0.14

Neutral

(source)

Varity_R

0.24

gMVP

0.52

Mutation Taster

=76/24

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over