7-131504431-A-G

Variant names:

• chr7-131504431-A-G
• rs2116773619
• NM_001018111.3:c.1557T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001018111.3(PODXL):​c.1557T>C​(p.Ser519Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PODXL NM_001018111.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 7-131504431-A-G is Benign according to our data. Variant chr7-131504431-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1546903.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.29 with no splicing effect.

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.1557T>C	p.Ser519Ser	synonymous	Exon 9 of 9	NP_001018121.1	O00592-1
	PODXL	NM_005397.4		c.1461T>C	p.Ser487Ser	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.1557T>C	p.Ser519Ser	synonymous	Exon 9 of 9	ENSP00000367817.3	O00592-1
	PODXL	ENST00000322985.9	TSL:1	c.1461T>C	p.Ser487Ser	synonymous	Exon 8 of 8	ENSP00000319782.9	O00592-2
	PODXL	ENST00000923671.1		c.1677T>C	p.Ser559Ser	synonymous	Exon 9 of 9	ENSP00000593730.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.0
DANN	Benign	0.61
PhyloP100		-1.3

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: rs2116773619; hg19: chr7-131189190;