rs749134415

Variant names:

• chr5-141854248-C-A
• rs749134415
• NM_032420.5:c.3508G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-141854248-C-A
• chr5-141854248-C-G
• chr5-141854248-C-T

Variant summary

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

The NM_032420.5(PCDH1):​c.3508G>T​(p.Gly1170Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH1	NM_032420.5	c.3508G>T	p.Gly1170Cys	missense_variant	Exon 5 of 5	ENST00000287008.8	NP_115796.2
PCDH1	XM_005268452.4	c.3556G>T	p.Gly1186Cys	missense_variant	Exon 5 of 5		XP_005268509.2
PCDH1	XM_017009517.3	c.2371G>T	p.Gly791Cys	missense_variant	Exon 4 of 4		XP_016865006.1
PCDH1	XM_005268454.6	c.*202G>T		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>T	p.Gly1170Cys	missense_variant	Exon 5 of 5	5	NM_032420.5	ENSP00000287008.3
PCDH1	ENST00000503492	c.*202G>T		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000424667.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.41	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.20		Loss of glycosylation at S1171 (P = 0.0762);
MVP		0.30
MPC		1.3
ClinPred		0.94	D
GERP RS		4.4
gMVP		0.65

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

LitVar

Other links and lift over

dbSNP: rs749134415; hg19: chr5-141233813;