1-155688109-G-A

Position:

• chr1-155688109-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001198903.1(YY1AP1):​c.356C>T​(p.Ser119Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000617 in 1,457,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. S119P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: YY1AP1 NM_001198903.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.277

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]

DAP3 (HGNC:2673): (death associated protein 3) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that also participates in apoptotic pathways which are initiated by tumor necrosis factor-alpha, Fas ligand, and gamma interferon. This protein potentially binds ATP/GTP and might be a functional partner of the mitoribosomal protein S27. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. Pseudogenes corresponding to this gene are found on chromosomes 1q and 2q. [provided by RefSeq, Dec 2010]

DAP3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09851915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YY1AP1	NM_139119.3	c.-59C>T		5_prime_UTR_variant	2/11	ENST00000355499.9	NP_620830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YY1AP1	ENST00000355499.9	c.-59C>T		5_prime_UTR_variant	2/11	1	NM_139119.3	ENSP00000347686.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248332 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134544

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 SAS exome AF: 0.0000332

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000617 AC: 9 AN: 1457808 Hom.: 0 Cov.: 30 AF XY: 0.00000690 AC XY: 5 AN XY: 724740

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000932

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

Bravo AF: 0.00000756

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

Apr 17, 2024

The c.356C>T (p.S119L) alteration is located in exon 1 (coding exon 1) of the YY1AP1 gene. This alteration results from a C to T substitution at nucleotide position 356, causing the serine (S) at amino acid position 119 to be replaced by a leucine (L). 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	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.00051	.;.;T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.52	T;T;T;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.099	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;.;N;.
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.027	.;D;T;D
Sift4G	Uncertain	0.030	D;D;T;D
Polyphen		0.0010	.;.;B;B
Vest4		0.16
MutPred		0.16		.;.;Loss of glycosylation at S47 (P = 0.0213);.;
MVP		0.20
MPC		0.15
ClinPred		0.55	D
GERP RS		2.9
Varity_R		0.14
gMVP		0.10

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

LitVar

Other links and lift over

dbSNP: rs1444870000; hg19: chr1-155657900; COSMIC: COSV105145143; COSMIC: COSV105145143;