chr1-155688099-A-G

Variant names:

• chr1-155688099-A-G
• rs76443098
• ENST00000368340.10:c.366T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001198903.1(YY1AP1):​c.366T>C​(p.Cys122Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00338 in 1,607,686 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (90 hom., cov: 29)
  • Exomes 𝑓: 0.0019 (85 hom.)
• Consequence: YY1AP1 NM_001198903.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.33
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 1-155688099-A-G is Benign according to our data. Variant chr1-155688099-A-G is described in ClinVar as Benign. ClinVar VariationId is 775608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.33 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

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.-49T>C		5_prime_UTR	Exon 2 of 11	NP_620830.1	Q9H869-2
	YY1AP1	NM_001198903.1		c.366T>C	p.Cys122Cys	synonymous	Exon 1 of 10	NP_001185832.1	Q9H869-9
	YY1AP1	NM_001198904.1		c.366T>C	p.Cys122Cys	synonymous	Exon 1 of 10	NP_001185833.1	Q9H869-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YY1AP1	ENST00000368340.10	TSL:1	c.366T>C	p.Cys122Cys	synonymous	Exon 1 of 10	ENSP00000357324.5	Q9H869-8
	YY1AP1	ENST00000405763.7	TSL:1	c.366T>C	p.Cys122Cys	synonymous	Exon 1 of 9	ENSP00000384583.3	B0QZ55
	YY1AP1	ENST00000355499.9	TSL:1 MANE Select	c.-49T>C		5_prime_UTR	Exon 2 of 11	ENSP00000347686.4	Q9H869-2

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 2696 AN: 152226 Hom.: 89 Cov.: 29

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00470 AC: 1158 AN: 246434 AF XY: 0.00359

Gnomad AFR exome AF: 0.0634

Gnomad AMR exome AF: 0.00176

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000242

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.00188 AC: 2737 AN: 1455342 Hom.: 85 Cov.: 30 AF XY: 0.00166 AC XY: 1204 AN XY: 723340

African (AFR) AF: 0.0647 AC: 2164 AN: 33428

American (AMR) AF: 0.00219 AC: 97 AN: 44312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25480

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.00136 AC: 116 AN: 85458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53136

Middle Eastern (MID) AF: 0.00209 AC: 12 AN: 5738

European-Non Finnish (NFE) AF: 0.000130 AC: 144 AN: 1108088

Other (OTH) AF: 0.00339 AC: 204 AN: 60090

GnomAD4 genome AF: 0.0177 AC: 2699 AN: 152344 Hom.: 90 Cov.: 29 AF XY: 0.0173 AC XY: 1288 AN XY: 74498

African (AFR) AF: 0.0621 AC: 2581 AN: 41578

American (AMR) AF: 0.00385 AC: 59 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68030

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.00800 Hom.: 18

Bravo AF: 0.0196

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Benign	0.87
PhyloP100		1.3
PromoterAI		-0.095	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=298/2	polymorphism (auto)

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: rs76443098; hg19: chr1-155657890;