Genetic Variant PARM1:p.Thr184Ile (chr4-75012932-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015393.4(PARM1):c.551C>T(p.Thr184Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PARM1
NM_015393.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.334

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04793328).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015393.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARM1	NM_015393.4	MANE Select	c.551C>T	p.Thr184Ile	missense	Exon 2 of 4	NP_056208.2	Q6UWI2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PARM1	ENST00000307428.7	TSL:1 MANE Select	c.551C>T	p.Thr184Ile	missense	Exon 2 of 4	ENSP00000370224.3	Q6UWI2
PARM1	ENST00000946485.1		c.740C>T	p.Thr247Ile	missense	Exon 4 of 6	ENSP00000616544.1
PARM1	ENST00000856900.1		c.656C>T	p.Thr219Ile	missense	Exon 3 of 5	ENSP00000526959.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249148

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461704

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111864

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.9

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.044

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.54

M_CAP

Benign

0.0068

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

PhyloP100

0.33

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.015

Sift

Benign

0.33

Sift4G

Benign

0.20

Polyphen

0.033

Vest4

0.060

MutPred

0.29

Loss of glycosylation at T184 (P = 0.0053)

MVP

0.16

MPC

0.15

ClinPred

0.039

GERP RS

2.3

Varity_R

0.039

gMVP

0.15

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over