rs544438419

Variant names:

• chr20-2794269-C-A
• rs544438419
• NM_019609.5:c.2126G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-2794269-C-A
• chr20-2794269-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019609.5(CPXM1):​c.2126G>T​(p.Arg709Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R709C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CPXM1 NM_019609.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.594
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13140997).

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.2126G>T	p.Arg709Leu	missense	Exon 14 of 14	NP_062555.1	Q96SM3
	CPXM1	NM_001184699.2		c.1904G>T	p.Arg635Leu	missense	Exon 14 of 14	NP_001171628.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPXM1	ENST00000380605.3	TSL:1 MANE Select	c.2126G>T	p.Arg709Leu	missense	Exon 14 of 14	ENSP00000369979.2	Q96SM3
	CPXM1	ENST00000921882.1		c.2126G>T	p.Arg709Leu	missense	Exon 14 of 14	ENSP00000591941.1
	CPXM1	ENST00000867057.1		c.2117G>T	p.Arg706Leu	missense	Exon 14 of 14	ENSP00000537116.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461778 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

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: 86254

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.59
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.046
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.0020	B
Vest4		0.40
MutPred		0.34		Loss of MoRF binding (P = 0.0061)
MVP		0.27
MPC		0.43
ClinPred		0.88	D
GERP RS		3.2
Varity_R		0.22
gMVP		0.66
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs544438419; hg19: chr20-2774915;