chr8-96785313-T-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016134.4(CPQ):​c.416T>A​(p.Ile139Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,454,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CPQ NM_016134.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.71

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34647924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPQ	NM_016134.4	c.416T>A	p.Ile139Asn	missense_variant	Exon 2 of 8	ENST00000220763.10	NP_057218.1
LOC124901985	XR_007061019.1	n.354+6229A>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPQ	ENST00000220763.10	c.416T>A	p.Ile139Asn	missense_variant	Exon 2 of 8	1	NM_016134.4	ENSP00000220763.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454846 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723050

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.068	T;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Pathogenic	2.9	M;.
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Benign	0.19
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.77	P;.
Vest4		0.44
MutPred		0.39		Loss of stability (P = 0.0174);Loss of stability (P = 0.0174);
MVP		0.53
MPC		0.39
ClinPred		0.99	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
gMVP		0.80

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-97797541;