NM_139119.3:c.1987G>C

Variant names:

• chr1-155659923-C-G
• rs1057519598
• NM_139119.3:c.1987G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139119.3(YY1AP1):​c.1987G>C​(p.Glu663Gln) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: YY1AP1 NM_139119.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46
• Publications: 1 publications found

Genes affected

YY1AP1 (HGNC:30935): (YY1 associated protein 1) Predicted to enable transcription coregulator activity. Involved in cell differentiation; cell population proliferation; and regulation of cell cycle. Located in fibrillar center and nucleoplasm. Colocalizes with Ino80 complex. [provided by Alliance of Genome Resources, Apr 2022]

YY1AP1 Gene-Disease associations (from GenCC):

• grange syndrome

  Inheritance: AR, AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21524337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YY1AP1	NM_139119.3	c.1987G>C	p.Glu663Gln	missense_variant	Exon 11 of 11	ENST00000355499.9	NP_620830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YY1AP1	ENST00000355499.9	c.1987G>C	p.Glu663Gln	missense_variant	Exon 11 of 11	1	NM_139119.3	ENSP00000347686.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	.;.;.;.;.;.;.;.;.;T;.
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;.;D;.;.;.;D;D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.22	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.4	.;.;.;.;.;.;.;.;.;M;.
PhyloP100		4.5
PROVEAN	Benign	-1.8	N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.070
Sift	Pathogenic	0.0	.;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.037	D;D;D;D;D;D;D;D;D;D;D
Polyphen		1.0, 0.97, 0.91	.;.;.;D;.;D;D;.;.;P;D
Vest4		0.39
MutPred		0.14		.;.;.;.;.;.;.;.;.;Loss of phosphorylation at S711 (P = 0.1102);.;
MVP		0.38
MPC		0.61
ClinPred		0.90	D
GERP RS		2.6
Varity_R		0.26
gMVP		0.42
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1057519598; hg19: chr1-155629714;