chr13-57641142-G-A

Variant names:

• chr13-57641142-G-A
• rs9527676
• NM_001040429.3:c.2565+6031G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040429.3(PCDH17):​c.2565+6031G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,518 control chromosomes in the GnomAD database, including 28,292 homozygotes. 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: 𝑓 0.60 (28292 hom., cov: 30)
• Consequence: PCDH17 NM_001040429.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07
• Publications: 3 publications found

Genes affected

PCDH17 (HGNC:14267): (protocadherin 17) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein contains six extracellular cadherin domains, a transmembrane domain, and a cytoplasmic tail differing from those of the classical cadherins. The encoded protein may play a role in the establishment and function of specific cell-cell connections in the brain. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH17	NM_001040429.3	c.2565+6031G>A		intron_variant	Intron 1 of 3	ENST00000377918.8	NP_001035519.1
PCDH17	XM_005266357.3	c.2565+6031G>A		intron_variant	Intron 2 of 4		XP_005266414.1
PCDH17	XM_047430276.1	c.2565+6031G>A		intron_variant	Intron 2 of 4		XP_047286232.1
PCDH17	XM_017020547.2	c.2565+6031G>A		intron_variant	Intron 1 of 3		XP_016876036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH17	ENST00000377918.8	c.2565+6031G>A		intron_variant	Intron 1 of 3	1	NM_001040429.3	ENSP00000367151.3
PCDH17	ENST00000484979.5	n.2565+6031G>A		intron_variant	Intron 1 of 3	1		ENSP00000432899.1
PCDH17	ENST00000612954.4	c.729+6031G>A		intron_variant	Intron 1 of 3	5		ENSP00000481329.1
PCDH17	ENST00000615375.1	c.99+6031G>A		intron_variant	Intron 1 of 4	4		ENSP00000483215.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91330 AN: 151402 Hom.: 28262 Cov.: 30

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.664

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.603 AC: 91415 AN: 151518 Hom.: 28292 Cov.: 30 AF XY: 0.607 AC XY: 44957 AN XY: 74048

African (AFR) AF: 0.462 AC: 19072 AN: 41316

American (AMR) AF: 0.681 AC: 10333 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2281 AN: 3460

East Asian (EAS) AF: 0.669 AC: 3429 AN: 5128

South Asian (SAS) AF: 0.752 AC: 3627 AN: 4824

European-Finnish (FIN) AF: 0.638 AC: 6724 AN: 10544

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.644 AC: 43684 AN: 67782

Other (OTH) AF: 0.665 AC: 1392 AN: 2094

Alfa AF: 0.601 Hom.: 8378

Bravo AF: 0.598

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.0
DANN	Benign	0.50
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs9527676; hg19: chr13-58215276; COSMIC: COSV64978391;