Variant chr4-75012704-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 -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 id is 770713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARM1	NM_015393.4 linkuse as main transcript	c.323G>C	p.Gly108Ala	missense_variant	2/4	ENST00000307428.7	NP_056208.2	Q6UWI2
PARM1	XM_011531833.1 linkuse as main transcript	c.428G>C	p.Gly143Ala	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.323G>C	p.Gly108Ala	missense_variant	2/4	1	NM_015393.4	ENSP00000370224.3	Q6UWI2
PARM1	ENST00000513238.5 linkuse as main transcript	c.44-21179G>C		intron_variant		3		ENSP00000424276.1	D6RBB6
ENSG00000248165	ENST00000513770.1 linkuse as main transcript	n.52-13533C>G		intron_variant		3

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

GnomAD3 exomes

AF:

0.00716

AC:

1783

AN:

249192

Hom.:

AF XY:

0.00738

AC XY:

998

AN XY:

135162

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 SAS exome

AF:

0.00284

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

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00559

Gnomad4 ASJ exome

AF:

0.0363

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00311

Gnomad4 FIN exome

AF:

0.00537

Gnomad4 NFE exome

AF:

0.00834

Gnomad4 OTH exome

AF:

0.00919

GnomAD4 genome

AF:

0.00602

AC:

917

AN:

152204

Hom.:

Cov.:

AF XY:

0.00590

AC XY:

439

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.00543

Gnomad4 ASJ

AF:

0.0360

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00518

Gnomad4 NFE

AF:

0.00794

Gnomad4 OTH

AF:

0.0104

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.6

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

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

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