chr1-155688077-G-A

Variant names:

• chr1-155688077-G-A
• rs1466553299
• NM_139119.3:c.-27C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PP3_Strong PP5_Moderate

The NM_139119.3(YY1AP1):​c.-27C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000698 in 1,432,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: YY1AP1 NM_139119.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.37
• 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]

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]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PP3: BayesDel_addAF computational evidence supports a deleterious effect, 0.576
• PP5: Variant 1-155688077-G-A is Pathogenic according to our data. Variant chr1-155688077-G-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 1723831.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-27C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	NP_620830.1	Q9H869-2
	YY1AP1	NM_139119.3	MANE Select	c.-27C>T		5_prime_UTR	Exon 2 of 11	NP_620830.1	Q9H869-2
	YY1AP1	NM_001198900.2		c.-19C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	NP_001185829.1	Q9H869-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YY1AP1	ENST00000355499.9	TSL:1 MANE Select	c.-27C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	ENSP00000347686.4	Q9H869-2
	YY1AP1	ENST00000359205.9	TSL:1	c.-19C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	ENSP00000352134.5	Q9H869-3
	YY1AP1	ENST00000361831.9	TSL:1	c.-141C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	ENSP00000355298.5	Q9H869-3

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000698 AC: 10 AN: 1432088 Hom.: 0 Cov.: 30 AF XY: 0.00000848 AC XY: 6 AN XY: 707942

African (AFR) AF: 0.00 AC: 0 AN: 32888

American (AMR) AF: 0.00 AC: 0 AN: 41944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24294

East Asian (EAS) AF: 0.00 AC: 0 AN: 39218

South Asian (SAS) AF: 0.00 AC: 0 AN: 83200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5642

European-Non Finnish (NFE) AF: 0.00000915 AC: 10 AN: 1093374

Other (OTH) AF: 0.00 AC: 0 AN: 59012

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.45
CADD	Benign	13
DANN	Uncertain	0.99
Eigen	Benign	0.18
Eigen_PC	Benign	-0.051
FATHMM_MKL	Benign	0.017	N
PhyloP100		1.4
Vest4		0.35
GERP RS		1.2
PromoterAI		-0.071	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=82/118	disease causing (fs/PTC)

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: rs1466553299; hg19: chr1-155657868;