chr1-155659815-G-T

Position:

• chr1-155659815-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000355499.9(YY1AP1):​c.2095C>A​(p.Arg699Ser) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R699C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: YY1AP1 ENST00000355499.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.165

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.021795213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YY1AP1	NM_139119.3	c.2095C>A	p.Arg699Ser	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.2095C>A	p.Arg699Ser	missense_variant	11/11	1	NM_139119.3	ENSP00000347686	A2
	ENST00000500626.2	n.431C>A		non_coding_transcript_exon_variant	1/9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jun 14, 2023

The c.2509C>A (p.R837S) alteration is located in exon 10 (coding exon 10) of the YY1AP1 gene. This alteration results from a C to A substitution at nucleotide position 2509, causing the arginine (R) at amino acid position 837 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	0.17
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.0
DANN	Benign	0.95
DEOGEN2	Benign	0.00079	.;.;.;.;.;.;.;.;.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.75	T;.;T;.;.;.;T;T;T;T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.022	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.090	.;.;.;.;.;.;.;.;.;N;.
MutationTaster	Benign	0.93	D;D;N;N;N;N;N;N;N;N;N;N;N;N
PROVEAN	Benign	0.95	N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.024
Sift	Benign	0.71	.;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.90	T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0040, 0.10, 0.92	.;.;.;B;.;B;B;.;.;P;B
Vest4		0.057
MutPred		0.24		.;.;.;.;.;.;.;.;.;Loss of stability (P = 0.0652);.;
MVP		0.095
MPC		0.17
ClinPred		0.18	T
GERP RS		-1.1
Varity_R		0.060
gMVP		0.15

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: chr1-155629606;