chr1-155660202-C-T

Position:

• chr1-155660202-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_139119.3(YY1AP1):​c.1708G>A​(p.Gly570Ser) 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. 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: 1.28

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35505295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YY1AP1	NM_139119.3	c.1708G>A	p.Gly570Ser	missense_variant	11/11	ENST00000355499.9	NP_620830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YY1AP1	ENST00000355499.9	c.1708G>A	p.Gly570Ser	missense_variant	11/11	1	NM_139119.3	ENSP00000347686	A2
	ENST00000500626.2	n.44G>A		non_coding_transcript_exon_variant	1/9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Dec 12, 2023

The c.2122G>A (p.G708S) alteration is located in exon 10 (coding exon 10) of the YY1AP1 gene. This alteration results from a G to A substitution at nucleotide position 2122, causing the glycine (G) at amino acid position 708 to be replaced by a serine (S). 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	Benign	0.085
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	.;.;.;.;.;.;.;.;.;T;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.89	D;.;D;.;.;.;D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.36	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	.;.;.;.;.;.;.;.;.;M;.
MutationTaster	Benign	1.0	D;D;N;N;N;N;N;N;N;N;N;N;N;N
PROVEAN	Uncertain	-3.2	D;D;D;D;D;D;D;D;D;D;D
REVEL	Benign	0.091
Sift	Uncertain	0.0080	.;D;D;D;D;D;D;D;D;D;D
Sift4G	Benign	0.10	T;D;D;T;T;T;D;T;D;D;T
Polyphen		1.0, 1.0	.;.;.;D;.;D;D;.;.;D;D
Vest4		0.20
MutPred		0.41		.;.;.;.;.;.;.;.;.;Gain of solvent accessibility (P = 0.2192);.;
MVP		0.44
MPC		0.49
ClinPred		0.96	D
GERP RS		2.5
Varity_R		0.11
gMVP		0.54

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: chr1-155629993;