14-100239253-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_003403.5(YY1):c.9G>A(p.Ser3=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000722 in 1,562,152 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00061 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00073 (2 hom.)
• Consequence: YY1 NM_003403.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.79

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 14-100239253-G-A is Benign according to our data. Variant chr14-100239253-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2644519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.8 with no splicing effect.
• BS2: High AC in GnomAd at 93 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YY1	NM_003403.5	c.9G>A	p.Ser3=	synonymous_variant	1/5	ENST00000262238.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YY1	ENST00000262238.10	c.9G>A	p.Ser3=	synonymous_variant	1/5	1	NM_003403.5	P1
YY1	ENST00000554371.1	c.9G>A	p.Ser3=	synonymous_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.000615 AC: 93 AN: 151304 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000728

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000669

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00120

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000758 AC: 129 AN: 170164 Hom.: 1 AF XY: 0.000727 AC XY: 68 AN XY: 93484

Gnomad AFR exome AF: 0.000114

Gnomad AMR exome AF: 0.0000368

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000550

Gnomad NFE exome AF: 0.00165

Gnomad OTH exome AF: 0.000426

GnomAD4 exome AF: 0.000734 AC: 1035 AN: 1410734 Hom.: 2 Cov.: 32 AF XY: 0.000686 AC XY: 479 AN XY: 698334

Gnomad4 AFR exome AF: 0.000126

Gnomad4 AMR exome AF: 0.0000523

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000423

Gnomad4 NFE exome AF: 0.000893

Gnomad4 OTH exome AF: 0.000615

GnomAD4 genome AF: 0.000614 AC: 93 AN: 151418 Hom.: 0 Cov.: 28 AF XY: 0.000635 AC XY: 47 AN XY: 73974

Gnomad4 AFR AF: 0.0000726

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000669

Gnomad4 NFE AF: 0.00120

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000494 Hom.: 0

Bravo AF: 0.000446

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

YY1: BP4, BP7 -

YY1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 21, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	11
Dann	Benign	0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs199591448; hg19: chr14-100705590;