Genetic Variant PYHIN1:p.Arg124Gly (chr1-158938501-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152501.5(PYHIN1):c.370C>G(p.Arg124Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000097 ( 0 hom. )

Consequence

PYHIN1
NM_152501.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0260

Publications

0 publications found

Variant links:

Genes affected

PYHIN1 (HGNC:28894): (pyrin and HIN domain family member 1) The protein encoded by this gene belongs to the HIN-200 family of interferon-inducible proteins that share a 200-amino acid signature motif at their C-termini. HIN200 proteins are primarily nuclear and are involved in transcriptional regulation of genes important for cell cycle control, differentiation, and apoptosis. Downregulation of this gene is associated with breast cancer. This protein acts as a tumor suppressor by promoting ubiquitination and subsequent degradation of MDM2, which leads to stabilization of p53/TP53. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

PYHIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04088515).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152501.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PYHIN1	NM_152501.5	MANE Select	c.370C>G	p.Arg124Gly	missense	Exon 3 of 9	NP_689714.2
PYHIN1	NM_198928.5		c.343C>G	p.Arg115Gly	missense	Exon 3 of 9	NP_945146.1	Q6K0P9-2
PYHIN1	NM_198929.5		c.370C>G	p.Arg124Gly	missense	Exon 3 of 8	NP_945147.1	Q6K0P9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PYHIN1	ENST00000368140.6	TSL:1 MANE Select	c.370C>G	p.Arg124Gly	missense	Exon 3 of 9	ENSP00000357122.1	Q6K0P9-1
PYHIN1	ENST00000368138.7	TSL:1	c.343C>G	p.Arg115Gly	missense	Exon 3 of 9	ENSP00000357120.3	Q6K0P9-2
PYHIN1	ENST00000392254.6	TSL:1	c.370C>G	p.Arg124Gly	missense	Exon 3 of 8	ENSP00000376083.2	Q6K0P9-3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000597

AC:

AN:

251454

AF XY:

0.0000368

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:

0.000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000971

AC:

142

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000935

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000125

AC:

139

AN:

1112006

Other (OTH)

AF:

0.0000331

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.0000460

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.000124

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.086

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.5

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.015

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.41

M_CAP

Benign

0.0031

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.69

PhyloP100

-0.026

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.0

REVEL

Benign

0.013

Sift

Benign

0.065

Sift4G

Benign

0.25

Polyphen

0.0

Vest4

0.080

MutPred

0.28

Loss of methylation at R124 (P = 0.027)

MVP

0.10

MPC

0.10

ClinPred

0.035

GERP RS

-4.6

Varity_R

0.040

gMVP

0.080

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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