14-100239450-GCCACCACCACCACCACCATCA-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_003403.5(YY1):c.221_241del(p.His74_His80del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000439 in 1,595,222 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: YY1 NM_003403.5 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.71

Genes affected

YY1 (HGNC:12856): (YY1 transcription factor) YY1 is a ubiquitously distributed transcription factor belonging to the GLI-Kruppel class of zinc finger proteins. The protein is involved in repressing and activating a diverse number of promoters. YY1 may direct histone deacetylases and histone acetyltransferases to a promoter in order to activate or repress the promoter, thus implicating histone modification in the function of YY1. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YY1	NM_003403.5	c.221_241del	p.His74_His80del	inframe_deletion	1/5	ENST00000262238.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YY1	ENST00000262238.10	c.221_241del	p.His74_His80del	inframe_deletion	1/5	1	NM_003403.5	P1

Frequencies

GnomAD3 genomes AF: 0.00000669 AC: 1 AN: 149510 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000415 AC: 6 AN: 1445596 Hom.: 0 AF XY: 0.00000696 AC XY: 5 AN XY: 718322

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000231

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000668 AC: 1 AN: 149626 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 73132

Gnomad4 AFR AF: 0.0000246

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Sep 18, 2023

Variant summary: YY1 c.221_241del21 (p.His74_His80del) results in an in-frame deletion that is predicted to remove 7 amino acids from the encoded protein. The variant was absent in 205146 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.221_241del21 in individuals affected with Gabriele De Vries Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs759320537; hg19: chr14-100705787;