4-30722030-G-T

Variant names:

• chr4-30722030-G-T
• rs933834191
• NM_001173523.2:c.608G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001173523.2(PCDH7):​c.608G>T​(p.Ser203Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000463 in 1,252,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: PCDH7 NM_001173523.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• Publications: 0 publications found

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:58750):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1636757).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001173523.2. 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
	PCDH7	NM_001173523.2	MANE Select	c.608G>T	p.Ser203Ile	missense	Exon 1 of 3	NP_001166994.1	A0A8Q3SI70
	PCDH7	NM_032457.4		c.608G>T	p.Ser203Ile	missense	Exon 1 of 3	NP_115833.2	A0A8V8TM73
	PCDH7	NM_002589.4		c.608G>T	p.Ser203Ile	missense	Exon 1 of 2	NP_002580.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH7	ENST00000695919.1	MANE Select	c.608G>T	p.Ser203Ile	missense	Exon 1 of 3	ENSP00000512266.1	A0A8Q3SI70
	PCDH7	ENST00000361762.3	TSL:1	c.608G>T	p.Ser203Ile	missense	Exon 1 of 2	ENSP00000355243.2	O60245-1
	PCDH7	ENST00000621961.2	TSL:5	c.608G>T	p.Ser203Ile	missense	Exon 1 of 4	ENSP00000484874.2	A0A087X2C4

Frequencies

GnomAD3 genomes AF: 0.000146 AC: 22 AN: 151034 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 1574 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000336 AC: 37 AN: 1101738 Hom.: 0 Cov.: 29 AF XY: 0.0000380 AC XY: 20 AN XY: 525728

African (AFR) AF: 0.0000440 AC: 1 AN: 22730

American (AMR) AF: 0.000121 AC: 1 AN: 8258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14366

East Asian (EAS) AF: 0.00 AC: 0 AN: 26360

South Asian (SAS) AF: 0.00 AC: 0 AN: 26088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2962

European-Non Finnish (NFE) AF: 0.0000332 AC: 31 AN: 934136

Other (OTH) AF: 0.0000904 AC: 4 AN: 44248

GnomAD4 genome AF: 0.000139 AC: 21 AN: 151140 Hom.: 0 Cov.: 33 AF XY: 0.000149 AC XY: 11 AN XY: 73848

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00125 AC: 19 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67728

Other (OTH) AF: 0.00 AC: 0 AN: 2098

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000223

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.073
Eigen_PC	Benign	0.063
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.77	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.3
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.17
Sift	Benign	0.059	T
Sift4G	Uncertain	0.011	D
Polyphen		0.57	P
Vest4		0.25
MutPred		0.33		Loss of phosphorylation at S203 (P = 0.0085)
MVP		0.37
ClinPred		0.48	T
GERP RS		4.6
PromoterAI		-0.25	Neutral
Varity_R		0.32
gMVP		0.44
Mutation Taster		=78/22	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: rs933834191; hg19: chr4-30723652;