4-30722174-C-T

Variant summary

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

The NM_001173523.2(PCDH7):​c.752C>T​(p.Thr251Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000043 in 1,395,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. T251N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

PCDH7
NM_001173523.2 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.11
Variant links:
Genes affected
PCDH7 (HGNC:8659): (protocadherin 7) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The gene encodes a protein with an extracellular domain containing 7 cadherin repeats. The gene product is an integral membrane protein that is thought to function in cell-cell recognition and adhesion. Alternative splicing yields isoforms with unique cytoplasmic tails. [provided by RefSeq, Jul 2008]

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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=0.137692).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCDH7NM_001173523.2 linkc.752C>T p.Thr251Ile missense_variant Exon 1 of 3 ENST00000695919.1 NP_001166994.1 A0A8Q3SI70
PCDH7NM_032457.4 linkc.752C>T p.Thr251Ile missense_variant Exon 1 of 3 NP_115833.2 A0A8V8TM73
PCDH7NM_002589.4 linkc.752C>T p.Thr251Ile missense_variant Exon 1 of 2 NP_002580.2 O60245-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCDH7ENST00000695919.1 linkc.752C>T p.Thr251Ile missense_variant Exon 1 of 3 NM_001173523.2 ENSP00000512266.1 A0A8Q3SI70

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000430
AC:
6
AN:
1395310
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
688150
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000556
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Uncertain
0.074
D
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.23
T;.
Eigen
Benign
-0.10
Eigen_PC
Benign
0.042
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.92
L;L
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-2.6
D;D
REVEL
Benign
0.24
Sift
Benign
0.053
T;T
Sift4G
Benign
0.18
T;T
Polyphen
0.20
B;.
Vest4
0.32
MutPred
0.43
Loss of phosphorylation at T251 (P = 0.0138);Loss of phosphorylation at T251 (P = 0.0138);
MVP
0.30
ClinPred
0.42
T
GERP RS
5.0
Varity_R
0.27
gMVP
0.57

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: chr4-30723796; API