7-131504383-C-A

Variant names:

• chr7-131504383-C-A
• rs34520552
• NM_001018111.3:c.1605G>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001018111.3(PODXL):​c.1605G>T​(p.Gly535Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,614,162 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (47 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (67 hom.)
• Consequence: PODXL NM_001018111.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.407
• Publications: 2 publications found

Genes affected

PODXL (HGNC:9171): (podocalyxin like) This gene encodes a member of the sialomucin protein family. The encoded protein was originally identified as an important component of glomerular podocytes. Podocytes are highly differentiated epithelial cells with interdigitating foot processes covering the outer aspect of the glomerular basement membrane. Other biological activities of the encoded protein include: binding in a membrane protein complex with Na+/H+ exchanger regulatory factor to intracellular cytoskeletal elements, playing a role in hematopoetic cell differentiation, and being expressed in vascular endothelium cells and binding to L-selectin. [provided by RefSeq, Jul 2008]

PODXL Gene-Disease associations (from GenCC):

• atypical juvenile parkinsonism

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• young-onset Parkinson disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 7-131504383-C-A is Benign according to our data. Variant chr7-131504383-C-A is described in ClinVar as Benign. ClinVar VariationId is 786111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.407 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018111.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PODXL	NM_001018111.3	MANE Select	c.1605G>T	p.Gly535Gly	synonymous	Exon 9 of 9	NP_001018121.1	O00592-1
	PODXL	NM_005397.4		c.1509G>T	p.Gly503Gly	synonymous	Exon 8 of 8	NP_005388.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PODXL	ENST00000378555.8	TSL:1 MANE Select	c.1605G>T	p.Gly535Gly	synonymous	Exon 9 of 9	ENSP00000367817.3	O00592-1
	PODXL	ENST00000322985.9	TSL:1	c.1509G>T	p.Gly503Gly	synonymous	Exon 8 of 8	ENSP00000319782.9	O00592-2
	PODXL	ENST00000923671.1		c.1725G>T	p.Gly575Gly	synonymous	Exon 9 of 9	ENSP00000593730.1

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2455 AN: 152168 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.0537

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00981

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00467 AC: 1174 AN: 251474 AF XY: 0.00349

Gnomad AFR exome AF: 0.0543

Gnomad AMR exome AF: 0.00492

Gnomad ASJ exome AF: 0.00228

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000633

Gnomad OTH exome AF: 0.00407

GnomAD4 exome AF: 0.00202 AC: 2947 AN: 1461876 Hom.: 67 Cov.: 31 AF XY: 0.00180 AC XY: 1306 AN XY: 727242

African (AFR) AF: 0.0562 AC: 1880 AN: 33480

American (AMR) AF: 0.00555 AC: 248 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00245 AC: 64 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53418

Middle Eastern (MID) AF: 0.00676 AC: 39 AN: 5768

European-Non Finnish (NFE) AF: 0.000388 AC: 432 AN: 1111998

Other (OTH) AF: 0.00460 AC: 278 AN: 60396

GnomAD4 genome AF: 0.0161 AC: 2455 AN: 152286 Hom.: 47 Cov.: 32 AF XY: 0.0156 AC XY: 1165 AN XY: 74468

African (AFR) AF: 0.0535 AC: 2223 AN: 41530

American (AMR) AF: 0.00973 AC: 149 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000617 AC: 42 AN: 68026

Other (OTH) AF: 0.0151 AC: 32 AN: 2116

Alfa AF: 0.00637 Hom.: 39

Bravo AF: 0.0183

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000533

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	6.4
DANN	Benign	0.72
PhyloP100		0.41
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34520552; hg19: chr7-131189142;