rs764257542

Variant names:

• chr20-2795673-C-A
• rs764257542
• NM_019609.5:c.1646G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-2795673-C-A
• chr20-2795673-C-G
• chr20-2795673-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_019609.5(CPXM1):​c.1646G>T​(p.Arg549Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R549Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CPXM1 NM_019609.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.88
• Publications: 0 publications found

Genes affected

CPXM1 (HGNC:15771): (carboxypeptidase X, M14 family member 1) This gene likely encodes a member of the carboxypeptidase family of proteins. Cloning of a comparable locus in mouse indicates that the encoded protein contains a discoidin domain and a carboxypeptidase domain, but the protein appears to lack residues necessary for carboxypeptidase activity.[provided by RefSeq, May 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.78

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019609.5. 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
	CPXM1	NM_019609.5	MANE Select	c.1646G>T	p.Arg549Leu	missense	Exon 11 of 14	NP_062555.1	Q96SM3
	CPXM1	NM_001184699.2		c.1498+148G>T		intron	N/A	NP_001171628.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPXM1	ENST00000380605.3	TSL:1 MANE Select	c.1646G>T	p.Arg549Leu	missense	Exon 11 of 14	ENSP00000369979.2	Q96SM3
	CPXM1	ENST00000921882.1		c.1646G>T	p.Arg549Leu	missense	Exon 11 of 14	ENSP00000591941.1
	CPXM1	ENST00000867057.1		c.1637G>T	p.Arg546Leu	missense	Exon 11 of 14	ENSP00000537116.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461696 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727166

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

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: 53252

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

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	Uncertain	0.46
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.9
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.23
Sift	Benign	0.082	T
Sift4G	Benign	0.29	T
Polyphen		0.75	P
Vest4		0.85
MutPred		0.43		Loss of disorder (P = 0.0383)
MVP		0.50
MPC		0.97
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.53
gMVP		0.80
Mutation Taster		=34/66	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs764257542; hg19: chr20-2776319;