4-75033897-A-C

Position:

• chr4-75033897-A-C

Variant summary

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

The NM_015393.4(PARM1):​c.784A>C​(p.Ile262Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.00042 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PARM1 NM_015393.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.59

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARM1	NM_015393.4	c.784A>C	p.Ile262Leu	missense_variant	3/4	ENST00000307428.7	NP_056208.2
PARM1	XM_011531833.1	c.889A>C	p.Ile297Leu	missense_variant	4/5		XP_011530135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARM1	ENST00000307428.7	c.784A>C	p.Ile262Leu	missense_variant	3/4	1	NM_015393.4	ENSP00000370224.3
PARM1	ENST00000513238.5	c.58A>C	p.Ile20Leu	missense_variant	2/3	3		ENSP00000424276.1
ENSG00000248165	ENST00000513770.1	n.51+877T>G		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000418 AC: 606 AN: 1449674 Hom.: 0 Cov.: 30 AF XY: 0.000384 AC XY: 276 AN XY: 719614

Gnomad4 AFR exome AF: 0.000540

Gnomad4 AMR exome AF: 0.0000230

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.000132

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000502

Gnomad4 OTH exome AF: 0.000250

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.784A>C (p.I262L) alteration is located in exon 3 (coding exon 3) of the PARM1 gene. This alteration results from a A to C substitution at nucleotide position 784, causing the isoleucine (I) at amino acid position 262 to be replaced by a leucine (L). 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	Pathogenic	0.68
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	.;D
Vest4		0.69
MutPred		0.29		.;Loss of sheet (P = 0.1398);
MVP		0.42
MPC		0.60
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.45
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-75959107;