3-127660427-C-T

Position:

• chr3-127660427-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PODXL2	NM_015720.4	c.399C>T	p.Thr133Thr	synonymous_variant	3/8	ENST00000342480.7	NP_056535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PODXL2	ENST00000342480.7	c.399C>T	p.Thr133Thr	synonymous_variant	3/8	1	NM_015720.4	ENSP00000345359.6

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24061 AN: 152056 Hom.: 1968 Cov.: 33

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

GnomAD3 exomes AF: 0.159 AC: 39558 AN: 248852 Hom.: 3275 AF XY: 0.160 AC XY: 21571 AN XY: 134732

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 SAS exome AF: 0.177

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.: 34 AF XY: 0.161 AC XY: 117116 AN XY: 726896

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.0991

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.158 AC: 24082 AN: 152174 Hom.: 1973 Cov.: 33 AF XY: 0.158 AC XY: 11741 AN XY: 74396

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.0933

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.152

Alfa AF: 0.159 Hom.: 2499

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
DANN	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs920232; hg19: chr3-127379270; COSMIC: COSV61065424;