dbSNP rs144921999: PARM1:p.Gly99Ser (chr4-75012676-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015393.4(PARM1):c.295G>A(p.Gly99Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00529 in 1,613,980 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 29 hom. )

Consequence

PARM1
NM_015393.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.824

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003514707).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARM1	NM_015393.4 link	c.295G>A	p.Gly99Ser	missense_variant	Exon 2 of 4	ENST00000307428.7	NP_056208.2	Q6UWI2
PARM1	XM_011531833.1 link	c.400G>A	p.Gly134Ser	missense_variant	Exon 3 of 5		XP_011530135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PARM1	ENST00000307428.7 link	c.295G>A	p.Gly99Ser	missense_variant	Exon 2 of 4	1	NM_015393.4	ENSP00000370224.3	Q6UWI2
PARM1	ENST00000513238.5 link	c.44-21207G>A		intron_variant	Intron 1 of 2	3		ENSP00000424276.1	D6RBB6
ENSG00000248165	ENST00000513770.1 link	n.52-13505C>T		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00332

AC:

505

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00547

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00317

AC:

790

AN:

249232

Hom.:

AF XY:

0.00303

AC XY:

410

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.00327

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00528

Gnomad OTH exome

AF:

0.00479

GnomAD4 exome

AF:

0.00549

AC:

8029

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00533

AC XY:

3879

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00351

Gnomad4 ASJ exome

AF:

0.00249

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000431

Gnomad4 NFE exome

AF:

0.00665

Gnomad4 OTH exome

AF:

0.00575

GnomAD4 genome

AF:

0.00332

AC:

505

AN:

152274

Hom.:

Cov.:

AF XY:

0.00300

AC XY:

223

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00104

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00547

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00440

Hom.:

Bravo

AF:

0.00340

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000725

AC:

ESP6500EA

AF:

0.00679

AC:

ExAC

AF:

0.00314

AC:

380

EpiCase

AF:

0.00513

EpiControl

AF:

0.00522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0061

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.50

M_CAP

Benign

0.011

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.6

REVEL

Benign

0.070

Sift

Benign

0.64

Sift4G

Benign

0.60

Polyphen

0.79

Vest4

0.065

MVP

0.40

MPC

0.51

ClinPred

0.018

GERP RS

4.5

Varity_R

0.059

gMVP

0.18

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over