Genetic Variant PODXL2:p.Thr133Thr (chr3-127660427-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_015720.4(PODXL2):c.399C>T(p.Thr133Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,613,424 control chromosomes in the GnomAD database, including 21,202 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 0.16 ( 1973 hom., cov: 33)

Exomes 𝑓: 0.16 ( 19229 hom. )

Consequence

PODXL2
NM_015720.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0480

Publications

15 publications found

Variant links:

Genes affected

PODXL2 (HGNC:17936): (podocalyxin like 2) This gene is a member of the CD34 family of cell surface transmembrane proteins, which are characterized by an N-terminal extracellular mucin domain, globular and stalk domains, a single pass transmembrane region, and a charged cytoplasmic tail. The encoded protein is a ligand for vascular selectins. [provided by RefSeq, Oct 2012]

PODXL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP7

Synonymous conserved (PhyloP=-0.048 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PODXL2	NM_015720.4 link	c.399C>T	p.Thr133Thr	synonymous_variant	Exon 3 of 8	ENST00000342480.7	NP_056535.1	Q9NZ53-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PODXL2	ENST00000342480.7 link	c.399C>T	p.Thr133Thr	synonymous_variant	Exon 3 of 8	1	NM_015720.4	ENSP00000345359.6		Q9NZ53-1

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24061

AN:

152056

Hom.:

1968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.0933

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.153

GnomAD2 exomes

AF:

0.159

AC:

39558

AN:

248852

AF XY:

0.160

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.180

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.0937

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.160

GnomAD4 exome

AF:

0.160

AC:

234010

AN:

1461250

Hom.:

19229

Cov.:

AF XY:

0.161

AC XY:

117116

AN XY:

726896

show subpopulations

African (AFR)

AF:

0.153

AC:

5135

AN:

33462

American (AMR)

AF:

0.180

AC:

8059

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

3892

AN:

26132

East Asian (EAS)

AF:

0.195

AC:

7722

AN:

39688

South Asian (SAS)

AF:

0.178

AC:

15339

AN:

86248

European-Finnish (FIN)

AF:

0.0991

AC:

5295

AN:

53414

Middle Eastern (MID)

AF:

0.126

AC:

727

AN:

5768

European-Non Finnish (NFE)

AF:

0.160

AC:

178155

AN:

1111470

Other (OTH)

AF:

0.160

AC:

9686

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

10145

20291

30436

40582

50727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6408

12816

19224

25632

32040

<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:

0.158

AC:

24082

AN:

152174

Hom.:

1973

Cov.:

AF XY:

0.158

AC XY:

11741

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.157

AC:

6498

AN:

41504

American (AMR)

AF:

0.205

AC:

3137

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.152

AC:

529

AN:

3472

East Asian (EAS)

AF:

0.176

AC:

912

AN:

5170

South Asian (SAS)

AF:

0.173

AC:

832

AN:

4814

European-Finnish (FIN)

AF:

0.0933

AC:

989

AN:

10596

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10790

AN:

67994

Other (OTH)

AF:

0.152

AC:

321

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1026

2052

3079

4105

5131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.159

Hom.:

3126

Bravo

AF:

0.165

Asia WGS

AF:

0.167

AC:

579

AN:

3478

EpiCase

AF:

0.159

EpiControl

AF:

0.163

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.4

(source)

DANN

Benign

0.72

PhyloP100

-0.048

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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