5-141854248-C-G

Variant names:

• chr5-141854248-C-G
• NM_032420.5:c.3508G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032420.5(PCDH1):​c.3508G>C​(p.Gly1170Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,338 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. G1170S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PCDH1 NM_032420.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.49

Genes affected

PCDH1 (HGNC:8655): (protocadherin 1) This gene belongs to the protocadherin subfamily within the cadherin superfamily. The encoded protein is a membrane protein found at cell-cell boundaries. It is involved in neural cell adhesion, suggesting a possible role in neuronal development. The protein includes an extracelllular region, containing 7 cadherin-like domains, a transmembrane region and a C-terminal cytoplasmic region. Cells expressing the protein showed cell aggregation activity. Alternative splicing occurs in this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36792672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH1	NM_032420.5	c.3508G>C	p.Gly1170Arg	missense_variant	Exon 5 of 5	ENST00000287008.8	NP_115796.2
PCDH1	XM_005268452.4	c.3556G>C	p.Gly1186Arg	missense_variant	Exon 5 of 5		XP_005268509.2
PCDH1	XM_017009517.3	c.2371G>C	p.Gly791Arg	missense_variant	Exon 4 of 4		XP_016865006.1
PCDH1	XM_005268454.6	c.*202G>C		3_prime_UTR_variant	Exon 6 of 6		XP_005268511.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH1	ENST00000287008.8	c.3508G>C	p.Gly1170Arg	missense_variant	Exon 5 of 5	5	NM_032420.5	ENSP00000287008.3
PCDH1	ENST00000503492	c.*202G>C		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000424667.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459338 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725826

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.52	T
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.38
MutPred		0.22		Loss of glycosylation at S1171 (P = 0.0596);
MVP		0.15
MPC		1.4
ClinPred		0.96	D
GERP RS		4.4
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: chr5-141233813;