rs751928165

Variant names:

• chr8-96785313-T-C
• rs751928165
• NM_016134.4:c.416T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-96785313-T-C
• chr8-96785313-T-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016134.4(CPQ):​c.416T>C​(p.Ile139Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000404 in 1,607,022 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. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: CPQ NM_016134.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 5.71
• 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]

LOC124901985 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.14677033).

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.416T>C	p.Ile139Thr	missense	Exon 2 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.416T>C	p.Ile139Thr	missense	Exon 2 of 8	ENSP00000220763.5	Q9Y646
	CPQ	ENST00000960277.1		c.416T>C	p.Ile139Thr	missense	Exon 2 of 9	ENSP00000630336.1
	CPQ	ENST00000863818.1		c.416T>C	p.Ile139Thr	missense	Exon 2 of 9	ENSP00000533877.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000692 AC: 17 AN: 245762 AF XY: 0.0000902

Gnomad AFR exome AF: 0.0000627

Gnomad AMR exome AF: 0.000178

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000275

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000360

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000351 AC: 51 AN: 1454844 Hom.: 0 Cov.: 31 AF XY: 0.0000346 AC XY: 25 AN XY: 723048

African (AFR) AF: 0.0000603 AC: 2 AN: 33174

American (AMR) AF: 0.0000911 AC: 4 AN: 43894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25716

East Asian (EAS) AF: 0.0000759 AC: 3 AN: 39504

South Asian (SAS) AF: 0.0000466 AC: 4 AN: 85784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53186

Middle Eastern (MID) AF: 0.000701 AC: 4 AN: 5706

European-Non Finnish (NFE) AF: 0.0000307 AC: 34 AN: 1107860

Other (OTH) AF: 0.00 AC: 0 AN: 60020

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74340

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.000459 AC: 7 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000567 Hom.: 0

Bravo AF: 0.0000793

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.21
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		5.7
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.13
Sift	Benign	0.051	T
Sift4G	Uncertain	0.059	T
Polyphen		0.015	B
Vest4		0.47
MVP		0.45
MPC		0.16
ClinPred		0.13	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.69
Mutation Taster		=80/20	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: rs751928165; hg19: chr8-97797541;