4-75012761-C-T

Variant names:

• chr4-75012761-C-T
• rs3822109
• NM_015393.4:c.380C>T

Variant summary

Our verdict is Benign. The variant received -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. 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 0.38 (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
• Publications: 35 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARM1	NM_015393.4	MANE Select	c.380C>T	p.Ser127Leu	missense	Exon 2 of 4	NP_056208.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARM1	ENST00000307428.7	TSL:1 MANE Select	c.380C>T	p.Ser127Leu	missense	Exon 2 of 4	ENSP00000370224.3
	PARM1	ENST00000513238.5	TSL:3	c.44-21122C>T		intron	N/A	ENSP00000424276.1
	ENSG00000248165	ENST00000513770.1	TSL:3	n.52-13590G>A		intron	N/A

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

GnomAD2 exomes AF: 0.387 AC: 96331 AN: 249070 AF XY: 0.393

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 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

African (AFR) AF: 0.304 AC: 10169 AN: 33480

American (AMR) AF: 0.293 AC: 13123 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 7362 AN: 26136

East Asian (EAS) AF: 0.145 AC: 5769 AN: 39700

South Asian (SAS) AF: 0.457 AC: 39425 AN: 86258

European-Finnish (FIN) AF: 0.484 AC: 25849 AN: 53396

Middle Eastern (MID) AF: 0.307 AC: 1768 AN: 5768

European-Non Finnish (NFE) AF: 0.448 AC: 497594 AN: 1111752

Other (OTH) AF: 0.399 AC: 24096 AN: 60370

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

African (AFR) AF: 0.310 AC: 12853 AN: 41442

American (AMR) AF: 0.345 AC: 5262 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 940 AN: 3462

East Asian (EAS) AF: 0.166 AC: 853 AN: 5154

South Asian (SAS) AF: 0.450 AC: 2164 AN: 4804

European-Finnish (FIN) AF: 0.488 AC: 5135 AN: 10532

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30071 AN: 67946

Other (OTH) AF: 0.360 AC: 759 AN: 2110

Alfa AF: 0.411 Hom.: 44757

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 v4.9

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
PhyloP100		-0.40
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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