17-31853006-T-C

Variant names:

• chr17-31853006-T-C
• NM_018405.4:c.191A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018405.4(COPRS):​c.191A>G​(p.Asn64Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COPRS NM_018405.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0600

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05692342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COPRS	NM_018405.4	c.191A>G	p.Asn64Ser	missense_variant	Exon 3 of 4	ENST00000302362.11	NP_060875.2
COPRS	NM_001330176.2	c.155A>G	p.Asn52Ser	missense_variant	Exon 3 of 4		NP_001317105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COPRS	ENST00000302362.11	c.191A>G	p.Asn64Ser	missense_variant	Exon 3 of 4	1	NM_018405.4	ENSP00000304327.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461640 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727148

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.191A>G (p.N64S) alteration is located in exon 3 (coding exon 3) of the COPRS gene. This alteration results from a A to G substitution at nucleotide position 191, causing the asparagine (N) at amino acid position 64 to be replaced by a serine (S). 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	0.068
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.0
DANN	Benign	0.33
DEOGEN2	Benign	0.017	T;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N;N;.
REVEL	Benign	0.027
Sift	Benign	0.19	T;T;.
Sift4G	Benign	0.14	T;T;.
Polyphen		0.0070	B;.;.
Vest4		0.14
MutPred		0.086		Gain of phosphorylation at N64 (P = 0.0175);.;.;
MVP		0.32
MPC		0.078
ClinPred		0.044	T
GERP RS		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.027
gMVP		0.025

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: chr17-30180025;