ENST00000368340.9:c.196T>C

Variant names:

• chr1-155688269-A-G
• rs114089731
• ENST00000368340.10:c.196T>C

Variant summary

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

The ENST00000368340.10(YY1AP1):​c.196T>C​(p.Ser66Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000657 in 1,597,372 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0033 (2 hom., cov: 29)
  • Exomes 𝑓: 0.00038 (3 hom.)
• Consequence: YY1AP1 ENST00000368340.10 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.38
• Publications: 2 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]

LOC124904430 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005141318).
• BP6: Variant 1-155688269-A-G is Benign according to our data. Variant chr1-155688269-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 791223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00326 (496/152324) while in subpopulation AFR AF = 0.0113 (470/41576). AF 95% confidence interval is 0.0105. There are 2 homozygotes in GnomAd4. There are 220 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000368340.10. 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.-151-68T>C		intron	N/A	NP_620830.1	Q9H869-2
	YY1AP1	NM_001198903.1		c.196T>C	p.Ser66Pro	missense	Exon 1 of 10	NP_001185832.1	Q9H869-9
	YY1AP1	NM_001198904.1		c.196T>C	p.Ser66Pro	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.196T>C	p.Ser66Pro	missense	Exon 1 of 10	ENSP00000357324.5	Q9H869-8
	YY1AP1	ENST00000405763.7	TSL:1	c.196T>C	p.Ser66Pro	missense	Exon 1 of 9	ENSP00000384583.3	B0QZ55
	YY1AP1	ENST00000355499.9	TSL:1 MANE Select	c.-151-68T>C		intron	N/A	ENSP00000347686.4	Q9H869-2

Frequencies

GnomAD3 genomes AF: 0.00325 AC: 495 AN: 152206 Hom.: 2 Cov.: 29

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000696 AC: 147 AN: 211262 AF XY: 0.000576

Gnomad AFR exome AF: 0.0105

Gnomad AMR exome AF: 0.000608

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000218

Gnomad OTH exome AF: 0.000376

GnomAD4 exome AF: 0.000383 AC: 553 AN: 1445048 Hom.: 3 Cov.: 30 AF XY: 0.000362 AC XY: 260 AN XY: 717694

African (AFR) AF: 0.0123 AC: 409 AN: 33202

American (AMR) AF: 0.000756 AC: 31 AN: 41008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25844

East Asian (EAS) AF: 0.00 AC: 0 AN: 39008

South Asian (SAS) AF: 0.0000943 AC: 8 AN: 84872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51298

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5750

European-Non Finnish (NFE) AF: 0.0000371 AC: 41 AN: 1104308

Other (OTH) AF: 0.000971 AC: 58 AN: 59758

GnomAD4 genome AF: 0.00326 AC: 496 AN: 152324 Hom.: 2 Cov.: 29 AF XY: 0.00295 AC XY: 220 AN XY: 74498

African (AFR) AF: 0.0113 AC: 470 AN: 41576

American (AMR) AF: 0.00124 AC: 19 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00154 Hom.: 1

Bravo AF: 0.00360

ExAC AF: 0.000815 AC: 98

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	YY1AP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	18
DANN	Benign	0.76
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-0.98	T
PhyloP100		1.4
PROVEAN	Benign	1.5	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.14
MVP		0.040
MPC		0.21
ClinPred		0.11	T
GERP RS		1.6
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
gMVP		0.039
Mutation Taster		=300/0	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: rs114089731; hg19: chr1-155658060; COSMIC: COSV55120113; COSMIC: COSV55120113;