Genetic Variant PIH1D2:p.Met230Ile (chr11-112070559-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_138789.4(PIH1D2):c.690G>A(p.Met230Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,614,036 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00057 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PIH1D2
NM_138789.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.519

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038762689).

BP6

Variant 11-112070559-C-T is Benign according to our data. Variant chr11-112070559-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2290404.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138789.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIH1D2	NM_138789.4	MANE Select	c.690G>A	p.Met230Ile	missense	Exon 5 of 6	NP_620144.1	Q8WWB5-1
PIH1D2	NM_001439211.1		c.690G>A	p.Met230Ile	missense	Exon 5 of 6	NP_001426140.1
PIH1D2	NM_001082619.2		c.690G>A	p.Met230Ile	missense	Exon 5 of 6	NP_001076088.1	Q8WWB5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIH1D2	ENST00000280350.10	TSL:5 MANE Select	c.690G>A	p.Met230Ile	missense	Exon 5 of 6	ENSP00000280350.4	Q8WWB5-1
PIH1D2	ENST00000532211.5	TSL:5	c.690G>A	p.Met230Ile	missense	Exon 5 of 6	ENSP00000431841.1	Q8WWB5-1
PIH1D2	ENST00000957365.1		c.690G>A	p.Met230Ile	missense	Exon 4 of 5	ENSP00000627424.1

Frequencies

GnomAD3 genomes

AF:

0.000565

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.0923

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251398

AF XY:

0.0000147

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1112004

Other (OTH)

AF:

0.0000331

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000565

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.000592

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.000688

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.0030

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.59

M_CAP

Benign

0.0042

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.4

PhyloP100

-0.52

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.22

REVEL

Benign

0.015

Sift

Benign

0.24

Sift4G

Benign

0.52

Polyphen

0.010

Vest4

0.085

MutPred

0.43

Gain of relative solvent accessibility (P = 0.0249)

MVP

0.25

MPC

0.12

ClinPred

0.039

GERP RS

1.6

Varity_R

0.074

gMVP

0.11

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over