rs149981793

Variant names:

• chr8-96785171-T-C
• NM_016134.4:c.274T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-96785171-T-C
• chr8-96785171-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016134.4(CPQ):​c.274T>C​(p.Tyr92His) 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 1,461,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 2.49

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12906623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPQ	NM_016134.4	c.274T>C	p.Tyr92His	missense_variant	Exon 2 of 8	ENST00000220763.10	NP_057218.1
LOC124901985	XR_007061019.1	n.354+6371A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPQ	ENST00000220763.10	c.274T>C	p.Tyr92His	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: 1461436 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727016

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

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	0.063
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.84
DEOGEN2	Benign	0.0090	T;T;T;T;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.58
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.56	T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;.;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.0	N;N;N;N;N
REVEL	Benign	0.074
Sift	Benign	0.27	T;T;T;T;T
Sift4G	Benign	0.34	T;T;T;T;T
Polyphen		0.0	B;.;.;.;.
Vest4		0.27
MutPred		0.42		Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);
MVP		0.15
MPC		0.15
ClinPred		0.26	T
GERP RS		2.0
Varity_R		0.082
gMVP		0.71

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: chr8-97797399;