3-111072150-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_015480.3(NECTIN3):​c.133C>T​(p.Pro45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000515 in 1,552,238 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00051 ( 7 hom. )

Consequence

NECTIN3
NM_015480.3 missense

Scores

1
2
15

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.20
Variant links:
Genes affected
NECTIN3 (HGNC:17664): (nectin cell adhesion molecule 3) This gene encodes a member of the nectin family of proteins, which function as adhesion molecules at adherens junctions. This family member interacts with other nectin-like proteins and with afadin, a filamentous actin-binding protein involved in the regulation of directional motility, cell proliferation and survival. This gene plays a role in ocular development involving the ciliary body. Mutations in this gene are believed to result in congenital ocular defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.007235378).
BP6
Variant 3-111072150-C-T is Benign according to our data. Variant chr3-111072150-C-T is described in ClinVar as [Benign]. Clinvar id is 3045238.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NECTIN3NM_015480.3 linkuse as main transcriptc.133C>T p.Pro45Ser missense_variant 1/6 ENST00000485303.6 NP_056295.1 Q9NQS3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NECTIN3ENST00000485303.6 linkuse as main transcriptc.133C>T p.Pro45Ser missense_variant 1/61 NM_015480.3 ENSP00000418070.1 Q9NQS3-1

Frequencies

GnomAD3 genomes
AF:
0.000519
AC:
79
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.0176
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00127
AC:
195
AN:
153590
Hom.:
3
AF XY:
0.00121
AC XY:
99
AN XY:
82086
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000804
Gnomad ASJ exome
AF:
0.0196
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000323
Gnomad OTH exome
AF:
0.00184
GnomAD4 exome
AF:
0.000514
AC:
720
AN:
1400094
Hom.:
7
Cov.:
33
AF XY:
0.000531
AC XY:
367
AN XY:
691030
show subpopulations
Gnomad4 AFR exome
AF:
0.0000634
Gnomad4 AMR exome
AF:
0.0000832
Gnomad4 ASJ exome
AF:
0.0191
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000124
Gnomad4 OTH exome
AF:
0.00174
GnomAD4 genome
AF:
0.000519
AC:
79
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.000430
AC XY:
32
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.0176
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.00112
Hom.:
3
Bravo
AF:
0.000620
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000482
AC:
4
ExAC
AF:
0.000437
AC:
48
Asia WGS
AF:
0.000289
AC:
1
AN:
3474

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

NECTIN3-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesNov 11, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.078
T;.
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.23
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.61
T;T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.0072
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-0.18
N;N
REVEL
Benign
0.073
Sift
Benign
0.090
T;D
Sift4G
Benign
0.20
T;D
Polyphen
0.23
B;.
Vest4
0.33
MVP
0.068
MPC
0.72
ClinPred
0.079
T
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.074
gMVP
0.34

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: rs200790665; hg19: chr3-110790997; API