Variant chr4-75012805-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015393.4(PARM1):c.424G>A(p.Ala142Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,613,880 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

PARM1
NM_015393.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.659

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0060917735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARM1	NM_015393.4 linkuse as main transcript	c.424G>A	p.Ala142Thr	missense_variant	2/4	ENST00000307428.7	NP_056208.2	Q6UWI2
PARM1	XM_011531833.1 linkuse as main transcript	c.529G>A	p.Ala177Thr	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.424G>A	p.Ala142Thr	missense_variant	2/4	1	NM_015393.4	ENSP00000370224.3	Q6UWI2
PARM1	ENST00000513238.5 linkuse as main transcript	c.44-21078G>A		intron_variant		3		ENSP00000424276.1	D6RBB6
ENSG00000248165	ENST00000513770.1 linkuse as main transcript	n.52-13634C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000149

AC:

AN:

248886

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135014

show subpopulations

Gnomad AFR exome

AF:

0.00181

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1461706

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000388

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000152

Hom.:

Bravo

AF:

0.000427

ESP6500AA

AF:

0.00210

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.000149

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2021

The c.424G>A (p.A142T) alteration is located in exon 2 (coding exon 2) of the PARM1 gene. This alteration results from a G to A substitution at nucleotide position 424, causing the alanine (A) at amino acid position 142 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.16

DANN

Benign

0.61

DEOGEN2

Benign

0.00074

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0088

LIST_S2

Benign

0.26

M_CAP

Benign

0.0067

MetaRNN

Benign

0.0061

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.010

REVEL

Benign

0.091

Sift

Benign

0.69

Sift4G

Benign

0.80

Polyphen

0.0010

Vest4

0.014

MVP

0.22

MPC

0.13

ClinPred

0.0047

GERP RS

-6.6

Varity_R

0.022

gMVP

0.11

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