Variant chr4-75013018-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015393.4(PARM1):c.637G>A(p.Glu213Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,872 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PARM1
NM_015393.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.196

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.083123416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARM1	NM_015393.4 linkuse as main transcript	c.637G>A	p.Glu213Lys	missense_variant	2/4	ENST00000307428.7	NP_056208.2	Q6UWI2
PARM1	XM_011531833.1 linkuse as main transcript	c.742G>A	p.Glu248Lys	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.637G>A	p.Glu213Lys	missense_variant	2/4	1	NM_015393.4	ENSP00000370224.3	Q6UWI2
PARM1	ENST00000513238.5 linkuse as main transcript	c.44-20865G>A		intron_variant		3		ENSP00000424276.1	D6RBB6
ENSG00000248165	ENST00000513770.1 linkuse as main transcript	n.52-13847C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

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

Sep 30, 2024

The c.637G>A (p.E213K) 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 637, causing the glutamic acid (E) at amino acid position 213 to be replaced by a lysine (K). 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

0.072

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.9

DANN

Benign

0.95

DEOGEN2

Benign

0.015

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.76

M_CAP

Benign

0.013

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.2

REVEL

Benign

0.0050

Sift

Benign

0.046

Sift4G

Benign

0.48

Polyphen

0.077

Vest4

0.16

MutPred

0.25

Gain of methylation at E213 (P = 8e-04);

MVP

0.34

MPC

0.15

ClinPred

0.048

GERP RS

2.7

Varity_R

0.034

gMVP

0.38

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