5-141864081-A-C

Variant names:

• chr5-141864081-A-C
• rs3797054
• NM_032420.5:c.2250T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_032420.5(PCDH1):​c.2250T>G​(p.Ala750Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCDH1 NM_032420.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.971
• Publications: 22 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.971 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032420.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH1	NM_032420.5	MANE Select	c.2250T>G	p.Ala750Ala	synonymous	Exon 3 of 5	NP_115796.2
	PCDH1	NM_001278613.2		c.2298T>G	p.Ala766Ala	synonymous	Exon 3 of 3	NP_001265542.1
	PCDH1	NM_002587.5		c.2250T>G	p.Ala750Ala	synonymous	Exon 3 of 3	NP_002578.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH1	ENST00000287008.8	TSL:5 MANE Select	c.2250T>G	p.Ala750Ala	synonymous	Exon 3 of 5	ENSP00000287008.3
	PCDH1	ENST00000394536.4	TSL:1	c.2250T>G	p.Ala750Ala	synonymous	Exon 3 of 3	ENSP00000378043.3
	PCDH1	ENST00000511044.1	TSL:1	n.1478T>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		-0.97

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: rs3797054; hg19: chr5-141243646;