rs778761077

Variant names:

• chr4-30722140-C-A
• NM_001173523.2:c.718C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-30722140-C-A
• chr4-30722140-C-G
• chr4-30722140-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001173523.2(PCDH7):​c.718C>A​(p.Arg240Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000762 in 1,312,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: PCDH7 NM_001173523.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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]

ENSG00000286596 (HGNC:):

ACMG classification

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=0.18530014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH7	NM_001173523.2	c.718C>A	p.Arg240Ser	missense_variant	Exon 1 of 3	ENST00000695919.1	NP_001166994.1
PCDH7	NM_032457.4	c.718C>A	p.Arg240Ser	missense_variant	Exon 1 of 3		NP_115833.2
PCDH7	NM_002589.4	c.718C>A	p.Arg240Ser	missense_variant	Exon 1 of 2		NP_002580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH7	ENST00000695919.1	c.718C>A	p.Arg240Ser	missense_variant	Exon 1 of 3		NM_001173523.2	ENSP00000512266.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.62e-7 AC: 1 AN: 1312672 Hom.: 0 Cov.: 33 AF XY: 0.00000156 AC XY: 1 AN XY: 641052

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000378

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: 0.00

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	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T;.
Eigen	Benign	-0.055
Eigen_PC	Benign	0.018
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.56	N;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.46	N;N
REVEL	Benign	0.27
Sift	Benign	0.042	D;T
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.97	D;.
Vest4		0.45
MutPred		0.42		Loss of solvent accessibility (P = 0.0238);Loss of solvent accessibility (P = 0.0238);
MVP		0.37
ClinPred		0.83	D
GERP RS		4.5
Varity_R		0.21
gMVP		0.58

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: chr4-30723762;