rs1131692046

Positions:

• chr14-100239779-A-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_003403.5(YY1):​c.535A>T​(p.Lys179Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 30)
• Consequence: YY1 NM_003403.5 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.42

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-100239779-A-T is Pathogenic according to our data. Variant chr14-100239779-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 430621.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YY1	NM_003403.5	c.535A>T	p.Lys179Ter	stop_gained	1/5	ENST00000262238.10	NP_003394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YY1	ENST00000262238.10	c.535A>T	p.Lys179Ter	stop_gained	1/5	1	NM_003403.5	ENSP00000262238	P1
YY1	ENST00000554804.1	c.22A>T	p.Lys8Ter	stop_gained	1/4	3		ENSP00000452225
YY1	ENST00000553625.5	c.28A>T	p.Lys10Ter	stop_gained	1/3	2		ENSP00000452140

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Gabriele de Vries syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 07, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.40	N
MutationTaster	Benign	1.0	A
Vest4		0.83
ClinPred		1.0	D
GERP RS		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs1131692046; hg19: chr14-100706116;