Variant 11-112067980-T-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_138789.4(PIH1D2):c.839A>T(p.Glu280Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,439,094 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: 30)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

PIH1D2
NM_138789.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Variant links:

Genes affected

PIH1D2 (HGNC:25210): (PIH1 domain containing 2) Enables small GTPase binding activity. Predicted to be involved in box C/D snoRNP assembly and rRNA processing. Predicted to be part of R2TP complex and ribonucleoprotein complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PIH1D2 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=0.17178416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIH1D2	NM_138789.4 linkuse as main transcript	c.839A>T	p.Glu280Val	missense_variant	6/6	ENST00000280350.10	NP_620144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIH1D2	ENST00000280350.10 linkuse as main transcript	c.839A>T	p.Glu280Val	missense_variant	6/6	5	NM_138789.4	ENSP00000280350	P1	Q8WWB5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000653

AC:

AN:

244842

Hom.:

AF XY:

0.0000832

AC XY:

AN XY:

132244

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000885

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:

0.0000125

AC:

AN:

1439094

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

716768

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000432

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000330

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

Feb 05, 2024

The c.839A>T (p.E280V) alteration is located in exon 6 (coding exon 5) of the PIH1D2 gene. This alteration results from a A to T substitution at nucleotide position 839, causing the glutamic acid (E) at amino acid position 280 to be replaced by a valine (V). 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

0.33

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

T;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.72

.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

0.81

D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.18

Sift

Uncertain

0.017

D;D

Sift4G

Uncertain

0.043

D;D

Polyphen

0.83

P;P

Vest4

0.37

MutPred

0.61

Gain of methylation at K281 (P = 0.0379);Gain of methylation at K281 (P = 0.0379);

MVP

0.42

MPC

0.45

ClinPred

0.86

GERP RS

5.5

Varity_R

0.14

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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