Variant 5-141945401-T-TGCTGCTGCTGCTGCTGCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_016580.4(PCDH12):c.3534_3535insGGCAGCAGCAGCAGCAGC(p.Ser1178_Ser1179insGlySerSerSerSerSer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 152,260 control chromosomes in the GnomAD database, including 44 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.020 ( 44 hom., cov: 33)

Exomes 𝑓: 0.027 ( 265 hom. )

Failed GnomAD Quality Control

Consequence

PCDH12
NM_016580.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.82

Variant links:

Genes affected

PCDH12 (HGNC:8657): (protocadherin 12) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 6 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene localizes to the region on chromosome 5 where the protocadherin gene clusters reside. The exon organization of this transcript is similar to that of the gene cluster transcripts, notably the first large exon, but no significant sequence homology exists. The function of this cellular adhesion protein is undetermined but mouse protocadherin 12 does not bind catenins and appears to have no affect on cell migration or growth. [provided by RefSeq, Jul 2008]

PCDH12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 5-141945401-T-TGCTGCTGCTGCTGCTGCC is Benign according to our data. Variant chr5-141945401-T-TGCTGCTGCTGCTGCTGCC is described in ClinVar as [Likely_benign]. Clinvar id is 773463.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0197 (2996/152260) while in subpopulation NFE AF= 0.0297 (2018/67998). AF 95% confidence interval is 0.0286. There are 44 homozygotes in gnomad4. There are 1441 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH12	NM_016580.4 linkuse as main transcript	c.3534_3535insGGCAGCAGCAGCAGCAGC	p.Ser1178_Ser1179insGlySerSerSerSerSer	conservative_inframe_insertion	4/4	ENST00000231484.4	NP_057664.1	Q9NPG4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH12	ENST00000231484.4 linkuse as main transcript	c.3534_3535insGGCAGCAGCAGCAGCAGC	p.Ser1178_Ser1179insGlySerSerSerSerSer	conservative_inframe_insertion	4/4	1	NM_016580.4	ENSP00000231484.3		Q9NPG4

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

2995

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00514

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00942

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.0468

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0297

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.0204

AC:

5046

AN:

247386

Hom.:

AF XY:

0.0209

AC XY:

2801

AN XY:

134210

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.00547

Gnomad ASJ exome

AF:

0.00697

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.0165

Gnomad FIN exome

AF:

0.0375

Gnomad NFE exome

AF:

0.0298

Gnomad OTH exome

AF:

0.0166

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0265

AC:

38724

AN:

1458770

Hom.:

265

Cov.:

AF XY:

0.0262

AC XY:

18997

AN XY:

725616

show subpopulations

Gnomad4 AFR exome

AF:

0.00368

Gnomad4 AMR exome

AF:

0.00573

Gnomad4 ASJ exome

AF:

0.00695

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0169

Gnomad4 FIN exome

AF:

0.0421

Gnomad4 NFE exome

AF:

0.0299

Gnomad4 OTH exome

AF:

0.0214

GnomAD4 genome

AF:

0.0197

AC:

2996

AN:

152260

Hom.:

Cov.:

AF XY:

0.0194

AC XY:

1441

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00512

Gnomad4 AMR

AF:

0.00941

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0154

Gnomad4 FIN

AF:

0.0468

Gnomad4 NFE

AF:

0.0297

Gnomad4 OTH

AF:

0.0124

Alfa

AF:

0.0128

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over