Genetic Variant NM_015720.4:c.399C>T (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:

Genome browser will be placed here

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over