rs3822109

Positions:

• chr4-75012761-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015393.4(PARM1):​c.380C>T​(p.Ser127Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,613,510 control chromosomes in the GnomAD database, including 148,830 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.38 (11690 hom., cov: 31)
  • Exomes 𝑓: 0.43 (137140 hom.)
• Consequence: PARM1 NM_015393.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397

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]

ENSG00000248165 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.10033354E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARM1	NM_015393.4	c.380C>T	p.Ser127Leu	missense_variant	2/4	ENST00000307428.7	NP_056208.2
PARM1	XM_011531833.1	c.485C>T	p.Ser162Leu	missense_variant	3/5		XP_011530135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARM1	ENST00000307428.7	c.380C>T	p.Ser127Leu	missense_variant	2/4	1	NM_015393.4	ENSP00000370224.3
PARM1	ENST00000513238.5	c.44-21122C>T		intron_variant		3		ENSP00000424276.1
ENSG00000248165	ENST00000513770.1	n.52-13590G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58366 AN: 151808 Hom.: 11678 Cov.: 31

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.363

GnomAD3 exomes AF: 0.387 AC: 96331 AN: 249070 Hom.: 19773 AF XY: 0.393 AC XY: 53133 AN XY: 135090

Gnomad AFR exome AF: 0.310

Gnomad AMR exome AF: 0.292

Gnomad ASJ exome AF: 0.276

Gnomad EAS exome AF: 0.169

Gnomad SAS exome AF: 0.460

Gnomad FIN exome AF: 0.483

Gnomad NFE exome AF: 0.433

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.428 AC: 625155 AN: 1461584 Hom.: 137140 Cov.: 52 AF XY: 0.428 AC XY: 311509 AN XY: 727084

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.457

Gnomad4 FIN exome AF: 0.484

Gnomad4 NFE exome AF: 0.448

Gnomad4 OTH exome AF: 0.399

GnomAD4 genome AF: 0.385 AC: 58416 AN: 151926 Hom.: 11690 Cov.: 31 AF XY: 0.386 AC XY: 28699 AN XY: 74286

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.360

Alfa AF: 0.416 Hom.: 22662

Bravo AF: 0.362

TwinsUK AF: 0.444 AC: 1645

ALSPAC AF: 0.439 AC: 1691

ESP6500AA AF: 0.311 AC: 1319

ESP6500EA AF: 0.432 AC: 3658

ExAC AF: 0.388 AC: 46942

Asia WGS AF: 0.281 AC: 979 AN: 3478

EpiCase AF: 0.428

EpiControl AF: 0.414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.79
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.00011	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.81	L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.020
Sift	Benign	1.0	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.017
MPC		0.12
ClinPred		0.0027	T
GERP RS		-3.3
Varity_R		0.020
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

Other links and lift over

dbSNP: rs3822109; hg19: chr4-75937971; COSMIC: COSV56650756;