chr4-75033900-A-C

Variant names:

• chr4-75033900-A-C
• NM_015393.4:c.787A>C

Variant summary

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

The NM_015393.4(PARM1):​c.787A>C​(p.Thr263Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PARM1 NM_015393.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.12

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 rank	MANE	Protein	UniProt
PARM1	NM_015393.4	c.787A>C	p.Thr263Pro	missense_variant	Exon 3 of 4	ENST00000307428.7	NP_056208.2
PARM1	XM_011531833.1	c.892A>C	p.Thr298Pro	missense_variant	Exon 4 of 5		XP_011530135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARM1	ENST00000307428.7	c.787A>C	p.Thr263Pro	missense_variant	Exon 3 of 4	1	NM_015393.4	ENSP00000370224.3
PARM1	ENST00000513238.5	c.61A>C	p.Thr21Pro	missense_variant	Exon 2 of 3	3		ENSP00000424276.1
ENSG00000248165	ENST00000513770.1	n.51+874T>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000234 AC: 340 AN: 1450298 Hom.: 0 Cov.: 30 AF XY: 0.000211 AC XY: 152 AN XY: 720024

Gnomad4 AFR exome AF: 0.000240

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000386

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.0000719

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000283

Gnomad4 OTH exome AF: 0.000167

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.787A>C (p.T263P) 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 787, causing the threonine (T) at amino acid position 263 to be replaced by a proline (P). 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	0.92
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	T;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	.;D
Vest4		0.72
MutPred		0.41		.;Loss of stability (P = 0.0626);
MVP		0.53
MPC		0.69
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.81
gMVP		0.86

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: chr4-75959110;