chr1-155659866-G-A

Variant names:

• chr1-155659866-G-A
• NM_139119.3:c.2044C>T

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.2044C>T​(p.Pro682Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: YY1AP1 NM_139119.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.554
• Publications: 0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

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=0.085327536).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139119.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YY1AP1	NM_139119.3	MANE Select	c.2044C>T	p.Pro682Ser	missense	Exon 11 of 11	NP_620830.1	Q9H869-2
	YY1AP1	NM_001198903.1		c.2458C>T	p.Pro820Ser	missense	Exon 10 of 10	NP_001185832.1	Q9H869-9
	YY1AP1	NM_001198904.1		c.2398C>T	p.Pro800Ser	missense	Exon 10 of 10	NP_001185833.1	Q9H869-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YY1AP1	ENST00000355499.9	TSL:1 MANE Select	c.2044C>T	p.Pro682Ser	missense	Exon 11 of 11	ENSP00000347686.4	Q9H869-2
	YY1AP1	ENST00000368340.10	TSL:1	c.2398C>T	p.Pro800Ser	missense	Exon 10 of 10	ENSP00000357324.5	Q9H869-8
	YY1AP1	ENST00000347088.9	TSL:1	c.2044C>T	p.Pro682Ser	missense	Exon 10 of 10	ENSP00000316079.6	Q9H869-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.0
DANN	Benign	0.59
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.10	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.55
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.047
Sift	Benign	0.20	T
Sift4G	Benign	0.13	T
Polyphen		0.31	B
Vest4		0.076
MutPred		0.14		Gain of phosphorylation at P728 (P = 0.0339)
MVP		0.20
MPC		0.16
ClinPred		0.030	T
GERP RS		1.6
Varity_R		0.023
gMVP		0.12
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr1-155629657;