14-100239258-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_003403.5(YY1):c.14A>C(p.Asp5Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 28)
• Consequence: YY1 NM_003403.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.33

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, YY1
• BP4: Computational evidence support a benign effect (MetaRNN=0.2339442).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YY1	NM_003403.5	c.14A>C	p.Asp5Ala	missense_variant	1/5	ENST00000262238.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YY1	ENST00000262238.10	c.14A>C	p.Asp5Ala	missense_variant	1/5	1	NM_003403.5	P1
YY1	ENST00000554371.1	c.14A>C	p.Asp5Ala	missense_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 28

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2021

The c.14A>C (p.D5A) alteration is located in exon 1 (coding exon 1) of the YY1 gene. This alteration results from a A to C substitution at nucleotide position 14, causing the aspartic acid (D) at amino acid position 5 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
Cadd	Uncertain	23
Dann	Benign	0.82
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.84	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.91	D
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-5.9	D;N
REVEL	Benign	0.22
Sift4G	Uncertain	0.060	T;T
Polyphen		0.0050	.;B
Vest4		0.40
MutPred		0.39		Gain of catalytic residue at S3 (P = 5e-04);Gain of catalytic residue at S3 (P = 5e-04);
MVP		0.39
MPC		1.4
ClinPred		0.96	D
GERP RS		1.5
Varity_R		0.17
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-100705595;