chr4-133150710-C-T

Variant names:

• chr4-133150710-C-T
• rs115170715
• NM_032961.3:c.570C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_032961.3(PCDH10):​c.570C>T​(p.Asp190Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000381 in 1,612,844 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (2 hom., cov: 30)
  • Exomes 𝑓: 0.00024 (2 hom.)
• Consequence: PCDH10 NM_032961.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.35
• Publications: 0 publications found

Genes affected

PCDH10 (HGNC:13404): (protocadherin 10) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. This family member contains 6 extracellular cadherin domains, a transmembrane domain and a cytoplasmic tail differing from those of the classical cadherins. The encoded protein is a cadherin-related neuronal receptor thought to function in the establishment of specific cell-cell connections in the brain. This gene plays a role in inhibiting cancer cell motility and cell migration. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]

PCDH10-DT (HGNC:53036): (PCDH10 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 4-133150710-C-T is Benign according to our data. Variant chr4-133150710-C-T is described in ClinVar as Benign. ClinVar VariationId is 731715.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.35 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032961.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH10	NM_032961.3	MANE Select	c.570C>T	p.Asp190Asp	synonymous	Exon 1 of 5	NP_116586.1	Q9P2E7-1
	PCDH10	NM_020815.3		c.570C>T	p.Asp190Asp	synonymous	Exon 1 of 1	NP_065866.1	Q9P2E7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH10	ENST00000264360.7	TSL:1 MANE Select	c.570C>T	p.Asp190Asp	synonymous	Exon 1 of 5	ENSP00000264360.4	Q9P2E7-1
	PCDH10	ENST00000618019.1	TSL:6	c.570C>T	p.Asp190Asp	synonymous	Exon 1 of 1	ENSP00000480512.1	Q9P2E7-2
	PCDH10-DT	ENST00000732819.1		n.219+141G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 260 AN: 151538 Hom.: 2 Cov.: 30

Gnomad AFR AF: 0.00602

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000395

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.000964

GnomAD2 exomes AF: 0.000448 AC: 112 AN: 249860 AF XY: 0.000303

Gnomad AFR exome AF: 0.00554

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000620

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000241 AC: 352 AN: 1461188 Hom.: 2 Cov.: 36 AF XY: 0.000208 AC XY: 151 AN XY: 726924

African (AFR) AF: 0.00726 AC: 243 AN: 33478

American (AMR) AF: 0.000425 AC: 19 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52922

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0000477 AC: 53 AN: 1111870

Other (OTH) AF: 0.000497 AC: 30 AN: 60384

GnomAD4 genome AF: 0.00173 AC: 262 AN: 151656 Hom.: 2 Cov.: 30 AF XY: 0.00170 AC XY: 126 AN XY: 74106

African (AFR) AF: 0.00607 AC: 251 AN: 41352

American (AMR) AF: 0.000394 AC: 6 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5086

South Asian (SAS) AF: 0.00 AC: 0 AN: 4782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67900

Other (OTH) AF: 0.000954 AC: 2 AN: 2096

Alfa AF: 0.000934 Hom.: 0

Bravo AF: 0.00189

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		3.3
Mutation Taster		=99/1	polymorphism

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: rs115170715; hg19: chr4-134071865;