4-75013043-C-G

Variant names:

• chr4-75013043-C-G
• rs371960515
• NM_015393.4:c.662C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015393.4(PARM1):​c.662C>G​(p.Pro221Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PARM1 NM_015393.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0773654).

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.662C>G	p.Pro221Arg	missense	Exon 2 of 4	NP_056208.2	Q6UWI2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARM1	ENST00000307428.7	TSL:1 MANE Select	c.662C>G	p.Pro221Arg	missense	Exon 2 of 4	ENSP00000370224.3	Q6UWI2
	PARM1	ENST00000946485.1		c.851C>G	p.Pro284Arg	missense	Exon 4 of 6	ENSP00000616544.1
	PARM1	ENST00000856900.1		c.767C>G	p.Pro256Arg	missense	Exon 3 of 5	ENSP00000526959.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

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: 0.000478

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 249164 AF XY: 0.00000740

Gnomad AFR exome AF: 0.000258

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: 0.00000410 AC: 6 AN: 1461670 Hom.: 0 Cov.: 41 AF XY: 0.00000275 AC XY: 2 AN XY: 727118

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111838

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74326

African (AFR) AF: 0.000193 AC: 8 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.000238 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.1
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.062
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.091	T
Polyphen		0.13	B
Vest4		0.14
MVP		0.48
MPC		0.14
ClinPred		0.10	T
GERP RS		4.5
Varity_R		0.15
gMVP		0.24
Mutation Taster		=85/15	polymorphism

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: rs371960515; hg19: chr4-75938253;