NM_024913.5:c.374C>A

Variant names:

• chr7-121015789-C-A
• rs752999333
• NM_024913.5:c.374C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024913.5(CPED1):​c.374C>A​(p.Thr125Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. T125M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CPED1 NM_024913.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 0 publications found

Genes affected

CPED1 (HGNC:26159): (cadherin like and PC-esterase domain containing 1) Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056320637).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024913.5. 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
	CPED1	NM_024913.5	MANE Select	c.374C>A	p.Thr125Lys	missense	Exon 3 of 23	NP_079189.4
	CPED1	NM_001105533.1		c.374C>A	p.Thr125Lys	missense	Exon 2 of 18	NP_001099003.1	Q9H6Q5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPED1	ENST00000310396.10	TSL:1 MANE Select	c.374C>A	p.Thr125Lys	missense	Exon 3 of 23	ENSP00000309772.5	A4D0V7-1
	CPED1	ENST00000450913.6	TSL:1	c.374C>A	p.Thr125Lys	missense	Exon 2 of 18	ENSP00000406122.2	A4D0V7-2
	CPED1	ENST00000495036.5	TSL:1	n.821C>A		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449396 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720644

African (AFR) AF: 0.00 AC: 0 AN: 32646

American (AMR) AF: 0.00 AC: 0 AN: 41216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25758

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39178

South Asian (SAS) AF: 0.00 AC: 0 AN: 83446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108222

Other (OTH) AF: 0.00 AC: 0 AN: 59888

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.1
DANN	Benign	0.96
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.15
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.064
Sift	Benign	0.67	T
Sift4G	Benign	0.70	T
Polyphen		0.59	P
Vest4		0.41
MutPred		0.44		Gain of ubiquitination at T125 (P = 0.0267)
MVP		0.081
MPC		0.074
ClinPred		0.13	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.051
gMVP		0.28
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs752999333; hg19: chr7-120655843; COSMIC: COSV60010443;