chr1-155676562-G-C

Variant names:

• chr1-155676562-G-C
• rs749232831
• NM_139119.3:c.310C>G

Variant summary

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

The NM_001198903.1(YY1AP1):​c.724C>G​(p.Gln242Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: YY1AP1 NM_001198903.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62
• Publications: 2 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=0.18030283).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198903.1. 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.310C>G	p.Gln104Glu	missense	Exon 5 of 11	NP_620830.1
	YY1AP1	NM_001198903.1		c.724C>G	p.Gln242Glu	missense	Exon 4 of 10	NP_001185832.1
	YY1AP1	NM_001198904.1		c.724C>G	p.Gln242Glu	missense	Exon 4 of 10	NP_001185833.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YY1AP1	ENST00000355499.9	TSL:1 MANE Select	c.310C>G	p.Gln104Glu	missense	Exon 5 of 11	ENSP00000347686.4
	YY1AP1	ENST00000368340.10	TSL:1	c.724C>G	p.Gln242Glu	missense	Exon 4 of 10	ENSP00000357324.5
	YY1AP1	ENST00000347088.9	TSL:1	c.310C>G	p.Gln104Glu	missense	Exon 4 of 10	ENSP00000316079.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251466 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions as Germline

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	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	T
Eigen	Benign	0.026
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.6
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.098
Sift	Benign	0.032	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.056	B
Vest4		0.43
MutPred		0.28		Gain of ubiquitination at K166 (P = 0.0353)
MVP		0.20
MPC		0.29
ClinPred		0.29	T
GERP RS		3.8
Varity_R		0.26
gMVP		0.32
Mutation Taster		=263/37	polymorphism

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

Other links and lift over

dbSNP: rs749232831; hg19: chr1-155646353;