NM_001407.3:c.9647C>T

Variant names:

• chr3-48639938-G-A
• rs1389951176
• NM_001407.3:c.9647C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 16/22 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 0 publications found

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]

CELSR3 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09141618).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001407.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELSR3	NM_001407.3	MANE Select	c.9647C>T	p.Ala3216Val	missense	Exon 34 of 35	NP_001398.2	Q9NYQ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELSR3	ENST00000164024.5	TSL:1 MANE Select	c.9647C>T	p.Ala3216Val	missense	Exon 34 of 35	ENSP00000164024.4	Q9NYQ7-1
	CELSR3	ENST00000461362.5	TSL:5	n.1735C>T		non_coding_transcript_exon	Exon 7 of 8
	CELSR3	ENST00000498057.1	TSL:2	n.3399C>T		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.2
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
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs1389951176; hg19: chr3-48677371;