chr1-13583851-C-T

Position:

• chr1-13583851-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_006474.5(PDPN):​c.-183C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00582 in 1,584,560 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (44 hom.)
• Consequence: PDPN NM_006474.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.01

Genes affected

PDPN (HGNC:29602): (podoplanin) This gene encodes a type-I integral membrane glycoprotein with diverse distribution in human tissues. The physiological function of this protein may be related to its mucin-type character. The homologous protein in other species has been described as a differentiation antigen and influenza-virus receptor. The specific function of this protein has not been determined but it has been proposed as a marker of lung injury. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047328174).
• BP6: Variant 1-13583851-C-T is Benign according to our data. Variant chr1-13583851-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 709645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDPN	NM_006474.5	c.-183C>T		5_prime_UTR_premature_start_codon_gain_variant	1/6	ENST00000621990.5	NP_006465.4
PDPN	NM_006474.5	c.-183C>T		5_prime_UTR_variant	1/6	ENST00000621990.5	NP_006465.4
PDPN	NM_198389.2	c.46C>T	p.Arg16Trp	missense_variant	1/6		NP_938203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDPN	ENST00000621990.5	c.-183C>T		5_prime_UTR_premature_start_codon_gain_variant	1/6	1	NM_006474.5	ENSP00000478125.1
PDPN	ENST00000621990.5	c.-183C>T		5_prime_UTR_variant	1/6	1	NM_006474.5	ENSP00000478125.1

Frequencies

GnomAD3 genomes AF: 0.00412 AC: 628 AN: 152250 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000940

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00619

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00531 AC: 1179 AN: 221832 Hom.: 5 AF XY: 0.00554 AC XY: 669 AN XY: 120664

Gnomad AFR exome AF: 0.00143

Gnomad AMR exome AF: 0.00257

Gnomad ASJ exome AF: 0.00252

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00772

Gnomad FIN exome AF: 0.00273

Gnomad NFE exome AF: 0.00767

Gnomad OTH exome AF: 0.00616

GnomAD4 exome AF: 0.00600 AC: 8593 AN: 1432192 Hom.: 44 Cov.: 31 AF XY: 0.00598 AC XY: 4251 AN XY: 711102

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00313

Gnomad4 ASJ exome AF: 0.00188

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00835

Gnomad4 FIN exome AF: 0.00243

Gnomad4 NFE exome AF: 0.00655

Gnomad4 OTH exome AF: 0.00611

GnomAD4 genome AF: 0.00412 AC: 628 AN: 152368 Hom.: 1 Cov.: 33 AF XY: 0.00391 AC XY: 291 AN XY: 74508

Gnomad4 AFR AF: 0.000938

Gnomad4 AMR AF: 0.00712

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.00619

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00535 Hom.: 7

Bravo AF: 0.00441

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00571 AC: 22

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00605 AC: 52

ExAC AF: 0.00579 AC: 703

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	PDPN: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.0
DANN	Uncertain	0.99
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.62	.;T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.0047	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	N;.;N
REVEL	Benign	0.067
Sift	Pathogenic	0.0	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.25	B;B;B
Vest4		0.12
MVP		0.27
MPC		0.43
ClinPred		0.069	T
GERP RS		0.19
gMVP		0.053

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

Publications

LitVar

Other links and lift over

dbSNP: rs113350533; hg19: chr1-13910346; COSMIC: COSV53847771; COSMIC: COSV53847771;