17-31859118-C-T

Variant names:

• chr17-31859118-C-T
• rs759708042
• NM_018405.4:c.82G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018405.4(COPRS):​c.82G>A​(p.Ala28Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000639 in 939,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: COPRS NM_018405.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52

Genes affected

COPRS (HGNC:28848): (coordinator of PRMT5 and differentiation stimulator) Enables histone binding activity. Involved in histone H4-R3 methylation. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.075448334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COPRS	NM_018405.4	c.82G>A	p.Ala28Thr	missense_variant	Exon 1 of 4	ENST00000302362.11	NP_060875.2
COPRS	NM_001330176.2	c.-298G>A		upstream_gene_variant			NP_001317105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COPRS	ENST00000302362.11	c.82G>A	p.Ala28Thr	missense_variant	Exon 1 of 4	1	NM_018405.4	ENSP00000304327.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000639 AC: 6 AN: 939020 Hom.: 0 Cov.: 32 AF XY: 0.00000451 AC XY: 2 AN XY: 443854

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000264

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000299

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.000280 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.82G>A (p.A28T) alteration is located in exon 1 (coding exon 1) of the COPRS gene. This alteration results from a G to A substitution at nucleotide position 82, causing the alanine (A) at amino acid position 28 to be replaced by a threonine (T). 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	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.37	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.018
Sift	Benign	0.037	D
Sift4G	Benign	0.11	T
Polyphen		0.10	B
Vest4		0.10
MutPred		0.21		Gain of phosphorylation at A28 (P = 0.0012);
MVP		0.32
MPC		0.091
ClinPred		0.19	T
GERP RS		-3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.047
gMVP		0.053

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: rs759708042; hg19: chr17-30186137;