Genetic Variant PARM1:p.Gly108Ala (chr4-75012704-G-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015393.4(PARM1):c.323G>C(p.Gly108Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00782 in 1,613,912 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0080 ( 86 hom. )

Consequence

PARM1
NM_015393.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.300

Publications

4 publications found

Variant links:

Genes affected

PARM1 (HGNC:24536): (prostate androgen-regulated mucin-like protein 1) Predicted to be involved in positive regulation of telomerase activity. Located in several cellular components, including Golgi apparatus; endosome; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PARM1 links:

ENSG00000248165 (HGNC:):

ENSG00000248165 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029345155).

BP6

Variant 4-75012704-G-C is Benign according to our data. Variant chr4-75012704-G-C is described in ClinVar as Benign. ClinVar VariationId is 770713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015393.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARM1	NM_015393.4	MANE Select	c.323G>C	p.Gly108Ala	missense	Exon 2 of 4	NP_056208.2	Q6UWI2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PARM1	ENST00000307428.7	TSL:1 MANE Select	c.323G>C	p.Gly108Ala	missense	Exon 2 of 4	ENSP00000370224.3	Q6UWI2
PARM1	ENST00000946485.1		c.512G>C	p.Gly171Ala	missense	Exon 4 of 6	ENSP00000616544.1
PARM1	ENST00000856900.1		c.428G>C	p.Gly143Ala	missense	Exon 3 of 5	ENSP00000526959.1

Frequencies

GnomAD3 genomes

AF:

0.00604

AC:

918

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00544

Gnomad ASJ

AF:

0.0360

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00518

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00794

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00716

AC:

1783

AN:

249192

AF XY:

0.00738

show subpopulations

Gnomad AFR exome

AF:

0.00116

Gnomad AMR exome

AF:

0.00542

Gnomad ASJ exome

AF:

0.0353

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00538

Gnomad NFE exome

AF:

0.00845

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.00801

AC:

11711

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00801

AC XY:

5824

AN XY:

727138

show subpopulations

African (AFR)

AF:

0.00116

AC:

AN:

33480

American (AMR)

AF:

0.00559

AC:

250

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0363

AC:

949

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00311

AC:

268

AN:

86258

European-Finnish (FIN)

AF:

0.00537

AC:

287

AN:

53402

Middle Eastern (MID)

AF:

0.0147

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00834

AC:

9278

AN:

1111866

Other (OTH)

AF:

0.00919

AC:

555

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

757

1515

2272

3030

3787

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.00602

AC:

917

AN:

152204

Hom.:

Cov.:

AF XY:

0.00590

AC XY:

439

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

41528

American (AMR)

AF:

0.00543

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0360

AC:

125

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00208

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00518

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00794

AC:

540

AN:

67994

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

100

150

200

250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0100

Hom.:

Bravo

AF:

0.00629

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00120

AC:

ESP6500EA

AF:

0.00952

AC:

ExAC

AF:

0.00688

AC:

833

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.0108

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.6

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0041

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.30

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.6

REVEL

Benign

0.016

Sift

Uncertain

0.029

Sift4G

Benign

0.78

Polyphen

0.36

Vest4

0.14

MVP

0.18

MPC

0.50

ClinPred

0.0030

GERP RS

-0.68

Varity_R

0.045

gMVP

0.17

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