NM_001407.3:c.9647C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001407.3(CELSR3):​c.9647C>T​(p.Ala3216Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3216D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

CELSR3
NM_001407.3 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20
Variant links:
Genes affected
CELSR3 (HGNC:3230): (cadherin EGF LAG seven-pass G-type receptor 3) This gene belongs to the flamingo subfamily, which is included in the cadherin superfamily. The flamingo cadherins consist of nonclassic-type cadherins that do not interact with catenins. They are plasma membrane proteins containing seven epidermal growth factor-like repeats, nine cadherin domains and two laminin A G-type repeats in their ectodomain. They also have seven transmembrane domains, a characteristic feature of their subfamily. The encoded protein may be involved in the regulation of contact-dependent neurite growth and may play a role in tumor formation. [provided by RefSeq, Jun 2013]

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ACMG classification

Classification made for transcript

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=0.09141618).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CELSR3NM_001407.3 linkc.9647C>T p.Ala3216Val missense_variant Exon 34 of 35 ENST00000164024.5 NP_001398.2 Q9NYQ7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CELSR3ENST00000164024.5 linkc.9647C>T p.Ala3216Val missense_variant Exon 34 of 35 1 NM_001407.3 ENSP00000164024.4 Q9NYQ7-1
CELSR3ENST00000461362.5 linkn.1735C>T non_coding_transcript_exon_variant Exon 7 of 8 5
CELSR3ENST00000498057.1 linkn.3399C>T non_coding_transcript_exon_variant Exon 3 of 4 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.60
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.091
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.55
N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.74
N
REVEL
Benign
0.11
Sift
Uncertain
0.023
D
Sift4G
Benign
0.14
T
Polyphen
0.0
B
Vest4
0.15
MutPred
0.094
Gain of relative solvent accessibility (P = 0.0479);
MVP
0.32
MPC
0.30
ClinPred
0.075
T
GERP RS
1.6
Varity_R
0.029
gMVP
0.086

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: chr3-48677371; API