Variant chr2-229025921-G-A 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_001100818.2(PID1):c.365C>T(p.Thr122Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

PID1
NM_001100818.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.41

Variant links:

Genes affected

PID1 (HGNC:26084): (phosphotyrosine interaction domain containing 1) Involved in several processes, including mitochondrion morphogenesis; negative regulation of phosphate metabolic process; and positive regulation of macromolecule metabolic process. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PID1 links:

PID1 (HGNC:):

PID1 links:

Genome browser will be placed here

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=0.15510815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PID1	NM_001100818.2 linkuse as main transcript	c.365C>T	p.Thr122Ile	missense_variant	3/3	ENST00000392055.8	NP_001094288.1	Q7Z2X4-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PID1	ENST00000392055.8 linkuse as main transcript	c.365C>T	p.Thr122Ile	missense_variant	3/3	2	NM_001100818.2	ENSP00000375908.3		Q7Z2X4-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251284

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000490

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000412

AC:

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

Mar 26, 2024

The c.458C>T (p.T153I) alteration is located in exon 4 (coding exon 3) of the PID1 gene. This alteration results from a C to T substitution at nucleotide position 458, causing the threonine (T) at amino acid position 153 to be replaced by an isoleucine (I). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

.;.;.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.0098

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.7

.;.;.;L

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.5

N;D;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.021

D;T;D;D

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

0.98

D;P;B;P

Vest4

0.35

MutPred

0.32

.;.;.;Loss of disorder (P = 0.0253);

MVP

0.39

MPC

0.39

ClinPred

0.28

GERP RS

5.5

Varity_R

0.19

gMVP

0.29

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