rs145853886

Variant names:

• chr8-96835000-C-G
• rs145853886
• NM_016134.4:c.461C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-96835000-C-G
• chr8-96835000-C-T

Variant summary

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

The NM_016134.4(CPQ):​c.461C>G​(p.Thr154Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. T154I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CPQ NM_016134.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.91
• Publications: 0 publications found

Genes affected

CPQ (HGNC:16910): (carboxypeptidase Q) This gene encodes a metallopeptidase that belongs to the peptidase M28 family. The encoded protein may catalyze the cleavage of dipeptides with unsubstituted terminals into amino acids. [provided by RefSeq, Jul 2013]

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=0.07549149).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016134.4. 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
	CPQ	NM_016134.4	MANE Select	c.461C>G	p.Thr154Ser	missense	Exon 3 of 8	NP_057218.1	Q9Y646

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPQ	ENST00000220763.10	TSL:1 MANE Select	c.461C>G	p.Thr154Ser	missense	Exon 3 of 8	ENSP00000220763.5	Q9Y646
	CPQ	ENST00000960277.1		c.461C>G	p.Thr154Ser	missense	Exon 3 of 9	ENSP00000630336.1
	CPQ	ENST00000863818.1		c.461C>G	p.Thr154Ser	missense	Exon 3 of 9	ENSP00000533877.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461038 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726840

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111624

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.58
DEOGEN2	Benign	0.00091	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.50	N
PhyloP100		2.9
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.065
Sift	Benign	0.78	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.47		Gain of disorder (P = 0.0478)
MVP		0.26
MPC		0.10
ClinPred		0.080	T
GERP RS		3.9
Varity_R		0.060
gMVP		0.32
Mutation Taster		=96/4	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: rs145853886; hg19: chr8-97847228;