Variant 16-31216782-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152901.4(PYDC1):c.247G>C(p.Ala83Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000964 in 1,452,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

PYDC1
NM_152901.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.38

Variant links:

Genes affected

PYDC1 (HGNC:30261): (pyrin domain containing 1) Predicted to enable cysteine-type endopeptidase activity. Involved in several processes, including negative regulation of tumor necrosis factor-mediated signaling pathway; regulation of gene expression; and tumor necrosis factor-mediated signaling pathway. Located in cytosol and nucleus. Part of IkappaB kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

PYDC1 links:

TRIM72 (HGNC:32671): (tripartite motif containing 72) Enables identical protein binding activity. Predicted to be involved in several processes, including cellular protein metabolic process; plasma membrane repair; and protein homooligomerization. Predicted to act upstream of or within negative regulation of insulin receptor signaling pathway; negative regulation of insulin-like growth factor receptor signaling pathway; and negative regulation of myotube differentiation. Predicted to be located in cytoplasmic vesicle membrane. Predicted to be active in cytoplasm and sarcolemma. [provided by Alliance of Genome Resources, Apr 2022]

TRIM72 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19996154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYDC1	NM_152901.4 link	c.247G>C	p.Ala83Pro	missense_variant	1/2	ENST00000302964.4	NP_690865.1	Q8WXC3
TRIM72	NM_001008274.4 link	c.390+1654C>G		intron_variant		ENST00000322122.8	NP_001008275.2	Q6ZMU5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYDC1	ENST00000302964.4 link	c.247G>C	p.Ala83Pro	missense_variant	1/2	1	NM_152901.4	ENSP00000304336.4		Q8WXC3
TRIM72	ENST00000322122.8 link	c.390+1654C>G		intron_variant		2	NM_001008274.4	ENSP00000312675.3		Q6ZMU5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248116

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134670

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000964

AC:

AN:

1452272

Hom.:

Cov.:

AF XY:

0.00000833

AC XY:

AN XY:

720442

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000382

Gnomad4 NFE exome

AF:

0.0000109

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.247G>C (p.A83P) alteration is located in exon 1 (coding exon 1) of the PYDC1 gene. This alteration results from a G to C substitution at nucleotide position 247, causing the alanine (A) at amino acid position 83 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.6

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.24

M_CAP

Benign

0.015

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.44

REVEL

Benign

0.042

Sift

Benign

0.12

Sift4G

Benign

0.26

Polyphen

0.79

Vest4

0.26

MutPred

0.51

Loss of MoRF binding (P = 0.0483);

MVP

0.61

MPC

1.7

ClinPred

0.27

GERP RS

0.69

Varity_R

0.17

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over