dbSNP rs3822109: PARM1:p.Ser127Leu (chr4-75012761-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015393.4(PARM1):c.380C>T(p.Ser127Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,613,510 control chromosomes in the GnomAD database, including 148,830 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 11690 hom., cov: 31)

Exomes 𝑓: 0.43 ( 137140 hom. )

Consequence

PARM1
NM_015393.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.397

Publications

35 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.10033354E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARM1	NM_015393.4 link	c.380C>T	p.Ser127Leu	missense_variant	Exon 2 of 4	ENST00000307428.7	NP_056208.2
PARM1	XM_011531833.1 link	c.485C>T	p.Ser162Leu	missense_variant	Exon 3 of 5		XP_011530135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PARM1	ENST00000307428.7 link	c.380C>T	p.Ser127Leu	missense_variant	Exon 2 of 4	1	NM_015393.4	ENSP00000370224.3
PARM1	ENST00000513238.5 link	c.44-21122C>T		intron_variant	Intron 1 of 2	3		ENSP00000424276.1
ENSG00000248165	ENST00000513770.1 link	n.52-13590G>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58366

AN:

151808

Hom.:

11678

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.488

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.363

GnomAD2 exomes

AF:

0.387

AC:

96331

AN:

249070

AF XY:

0.393

show subpopulations

Gnomad AFR exome

AF:

0.310

Gnomad AMR exome

AF:

0.292

Gnomad ASJ exome

AF:

0.276

Gnomad EAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.483

Gnomad NFE exome

AF:

0.433

Gnomad OTH exome

AF:

0.392

GnomAD4 exome

AF:

0.428

AC:

625155

AN:

1461584

Hom.:

137140

Cov.:

AF XY:

0.428

AC XY:

311509

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.304

AC:

10169

AN:

33480

American (AMR)

AF:

0.293

AC:

13123

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

7362

AN:

26136

East Asian (EAS)

AF:

0.145

AC:

5769

AN:

39700

South Asian (SAS)

AF:

0.457

AC:

39425

AN:

86258

European-Finnish (FIN)

AF:

0.484

AC:

25849

AN:

53396

Middle Eastern (MID)

AF:

0.307

AC:

1768

AN:

5768

European-Non Finnish (NFE)

AF:

0.448

AC:

497594

AN:

1111752

Other (OTH)

AF:

0.399

AC:

24096

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

23258

46515

69773

93030

116288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14828

29656

44484

59312

74140

<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:

0.385

AC:

58416

AN:

151926

Hom.:

11690

Cov.:

AF XY:

0.386

AC XY:

28699

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.310

AC:

12853

AN:

41442

American (AMR)

AF:

0.345

AC:

5262

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

940

AN:

3462

East Asian (EAS)

AF:

0.166

AC:

853

AN:

5154

South Asian (SAS)

AF:

0.450

AC:

2164

AN:

4804

European-Finnish (FIN)

AF:

0.488

AC:

5135

AN:

10532

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.443

AC:

30071

AN:

67946

Other (OTH)

AF:

0.360

AC:

759

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1798

3596

5394

7192

8990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<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:

0.411

Hom.:

44757

Bravo

AF:

0.362

TwinsUK

AF:

0.444

AC:

1645

ALSPAC

AF:

0.439

AC:

1691

ESP6500AA

AF:

0.311

AC:

1319

ESP6500EA

AF:

0.432

AC:

3658

ExAC

AF:

0.388

AC:

46942

Asia WGS

AF:

0.281

AC:

979

AN:

3478

EpiCase

AF:

0.428

EpiControl

AF:

0.414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.6

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0063

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.46

MetaRNN

Benign

0.00011

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.81

PhyloP100

-0.40

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.8

REVEL

Benign

0.020

Sift

Benign

1.0

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.017

MPC

0.12

ClinPred

0.0027

GERP RS

-3.3

Varity_R

0.020

gMVP

0.11

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over