1-155688145-C-T

Variant names:

• chr1-155688145-C-T
• rs61817761
• ENST00000368340.10:c.320G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001198903.1(YY1AP1):​c.320G>A​(p.Gly107Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 1,613,624 control chromosomes in the GnomAD database, including 264 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (12 hom., cov: 29)
  • Exomes 𝑓: 0.017 (252 hom.)
• Consequence: YY1AP1 NM_001198903.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.422
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0051515102).
• BP6: Variant 1-155688145-C-T is Benign according to our data. Variant chr1-155688145-C-T is described in ClinVar as Benign. ClinVar VariationId is 773115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0101 (1541/152340) while in subpopulation NFE AF = 0.0168 (1141/68030). AF 95% confidence interval is 0.016. There are 12 homozygotes in GnomAd4. There are 663 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR,AD gene

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.-95G>A		5_prime_UTR	Exon 2 of 11	NP_620830.1	Q9H869-2
	YY1AP1	NM_001198903.1		c.320G>A	p.Gly107Glu	missense	Exon 1 of 10	NP_001185832.1	Q9H869-9
	YY1AP1	NM_001198904.1		c.320G>A	p.Gly107Glu	missense	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.320G>A	p.Gly107Glu	missense	Exon 1 of 10	ENSP00000357324.5	Q9H869-8
	YY1AP1	ENST00000405763.7	TSL:1	c.320G>A	p.Gly107Glu	missense	Exon 1 of 9	ENSP00000384583.3	B0QZ55
	YY1AP1	ENST00000355499.9	TSL:1 MANE Select	c.-95G>A		5_prime_UTR	Exon 2 of 11	ENSP00000347686.4	Q9H869-2

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1542 AN: 152222 Hom.: 12 Cov.: 29

Gnomad AFR AF: 0.00403

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00896

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00593

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00928 AC: 2316 AN: 249446 AF XY: 0.00924

Gnomad AFR exome AF: 0.00273

Gnomad AMR exome AF: 0.00559

Gnomad ASJ exome AF: 0.00200

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00533

Gnomad NFE exome AF: 0.0162

Gnomad OTH exome AF: 0.00889

GnomAD4 exome AF: 0.0167 AC: 24475 AN: 1461284 Hom.: 252 Cov.: 30 AF XY: 0.0159 AC XY: 11554 AN XY: 726866

African (AFR) AF: 0.00296 AC: 99 AN: 33476

American (AMR) AF: 0.00595 AC: 266 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 68 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39690

South Asian (SAS) AF: 0.00181 AC: 156 AN: 86224

European-Finnish (FIN) AF: 0.00640 AC: 341 AN: 53290

Middle Eastern (MID) AF: 0.00157 AC: 9 AN: 5750

European-Non Finnish (NFE) AF: 0.0204 AC: 22648 AN: 1111678

Other (OTH) AF: 0.0147 AC: 887 AN: 60350

GnomAD4 genome AF: 0.0101 AC: 1541 AN: 152340 Hom.: 12 Cov.: 29 AF XY: 0.00890 AC XY: 663 AN XY: 74500

African (AFR) AF: 0.00402 AC: 167 AN: 41586

American (AMR) AF: 0.00895 AC: 137 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.00593 AC: 63 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0168 AC: 1141 AN: 68030

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.0107 Hom.: 10

Bravo AF: 0.0105

TwinsUK AF: 0.0135 AC: 50

ALSPAC AF: 0.0208 AC: 80

ESP6500AA AF: 0.00386 AC: 17

ESP6500EA AF: 0.0166 AC: 143

ExAC AF: 0.00913 AC: 1108

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0156

EpiControl AF: 0.0142

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
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.42
PROVEAN	Benign	2.6	N
REVEL	Benign	0.069
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.031	B
Vest4		0.14
MVP		0.16
MPC		0.44
ClinPred		0.086	T
GERP RS		1.8
PromoterAI		-0.058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.045
Mutation Taster		=91/9	polymorphism

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: rs61817761; hg19: chr1-155657936; COSMIC: COSV99803639; COSMIC: COSV99803639;