chr1-16451923-C-T

Variant summary

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

The NM_018090.5(NECAP2):​c.575C>T​(p.Pro192Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. P192R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

NECAP2
NM_018090.5 missense

Scores

6
8
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.90
Variant links:
Genes affected
NECAP2 (HGNC:25528): (NECAP endocytosis associated 2) This gene likely encodes a member of the adaptin-ear-binding coat-associated protein family. Studies of a similar protein in rat suggest a role in clathrin-mediated endocytosis. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NECAP2NM_018090.5 linkc.575C>T p.Pro192Leu missense_variant Exon 6 of 8 ENST00000337132.10 NP_060560.1 Q9NVZ3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NECAP2ENST00000337132.10 linkc.575C>T p.Pro192Leu missense_variant Exon 6 of 8 1 NM_018090.5 ENSP00000338746.5 Q9NVZ3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Uncertain
0.057
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
T;T;.;.
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
.;D;D;D
M_CAP
Benign
0.056
D
MetaRNN
Uncertain
0.72
D;D;D;D
MetaSVM
Uncertain
-0.26
T
MutationAssessor
Pathogenic
3.4
M;.;.;M
PrimateAI
Uncertain
0.48
T
PROVEAN
Pathogenic
-8.7
D;D;D;D
REVEL
Benign
0.24
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
0.98
D;.;D;D
Vest4
0.65
MutPred
0.22
Loss of glycosylation at P192 (P = 0.0071);.;.;Loss of glycosylation at P192 (P = 0.0071);
MVP
0.75
MPC
0.71
ClinPred
0.99
D
GERP RS
5.7
Varity_R
0.62
gMVP
0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs375487117; hg19: chr1-16778418; API