Variant 4-75012898-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015393.4(PARM1):c.517G>A(p.Val173Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000757 in 1,613,826 control chromosomes in the GnomAD database, including 3 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00085 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00075 ( 2 hom. )

Consequence

PARM1
NM_015393.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.04

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061292946).

BP6

Variant 4-75012898-G-A is Benign according to our data. Variant chr4-75012898-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2266683.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARM1	NM_015393.4 linkuse as main transcript	c.517G>A	p.Val173Ile	missense_variant	2/4	ENST00000307428.7	NP_056208.2	Q6UWI2
PARM1	XM_011531833.1 linkuse as main transcript	c.622G>A	p.Val208Ile	missense_variant	3/5		XP_011530135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PARM1	ENST00000307428.7 linkuse as main transcript	c.517G>A	p.Val173Ile	missense_variant	2/4	1	NM_015393.4	ENSP00000370224.3	Q6UWI2
PARM1	ENST00000513238.5 linkuse as main transcript	c.44-20985G>A		intron_variant		3		ENSP00000424276.1	D6RBB6
ENSG00000248165	ENST00000513770.1 linkuse as main transcript	n.52-13727C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000849

AC:

129

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000822

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.000591

AC:

147

AN:

248934

Hom.:

AF XY:

0.000666

AC XY:

AN XY:

135058

show subpopulations

Gnomad AFR exome

AF:

0.000710

Gnomad AMR exome

AF:

0.000840

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000869

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000747

AC:

1092

AN:

1461708

Hom.:

Cov.:

AF XY:

0.000751

AC XY:

546

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.000876

Gnomad4 OTH exome

AF:

0.000646

GnomAD4 genome

AF:

0.000848

AC:

129

AN:

152118

Hom.:

Cov.:

AF XY:

0.000874

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000820

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.000913

Hom.:

Bravo

AF:

0.000876

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000233

AC:

ESP6500EA

AF:

0.00129

AC:

ExAC

AF:

0.000561

AC:

EpiCase

AF:

0.00142

EpiControl

AF:

0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.045

DANN

Benign

0.49

DEOGEN2

Benign

0.00090

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.30

M_CAP

Benign

0.0047

MetaRNN

Benign

0.0061

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.11

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.20

REVEL

Benign

0.0050

Sift

Benign

0.59

Sift4G

Benign

0.54

Polyphen

0.0020

Vest4

0.036

MVP

0.11

MPC

0.11

ClinPred

0.000088

GERP RS

-4.2

Varity_R

0.0098

gMVP

0.059

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over