ENST00000368340.10:c.355T>C

Variant names:

• chr1-155688110-A-G
• rs143953255
• ENST00000368340.10:c.355T>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.355T>C​(p.Ser119Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0084 in 1,610,104 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S119L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0072 (6 hom., cov: 29)
  • Exomes 𝑓: 0.0085 (99 hom.)
• Consequence: YY1AP1 ENST00000368340.10 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.40
• Publications: 3 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=0.0037935078).
• BP6: Variant 1-155688110-A-G is Benign according to our data. Variant chr1-155688110-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 782734.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 = 0.0072 (1096/152288) while in subpopulation NFE AF = 0.00928 (631/68016). AF 95% confidence interval is 0.00868. There are 6 homozygotes in GnomAd4. There are 576 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 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.-60T>C		5_prime_UTR	Exon 2 of 11	NP_620830.1	Q9H869-2
	YY1AP1	NM_001198903.1		c.355T>C	p.Ser119Pro	missense	Exon 1 of 10	NP_001185832.1	Q9H869-9
	YY1AP1	NM_001198904.1		c.355T>C	p.Ser119Pro	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.355T>C	p.Ser119Pro	missense	Exon 1 of 10	ENSP00000357324.5	Q9H869-8
	YY1AP1	ENST00000405763.7	TSL:1	c.355T>C	p.Ser119Pro	missense	Exon 1 of 9	ENSP00000384583.3	B0QZ55
	YY1AP1	ENST00000355499.9	TSL:1 MANE Select	c.-60T>C		5_prime_UTR	Exon 2 of 11	ENSP00000347686.4	Q9H869-2

Frequencies

GnomAD3 genomes AF: 0.00722 AC: 1098 AN: 152170 Hom.: 6 Cov.: 29

Gnomad AFR AF: 0.00500

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00928

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00684 AC: 1699 AN: 248404 AF XY: 0.00678

Gnomad AFR exome AF: 0.00473

Gnomad AMR exome AF: 0.00283

Gnomad ASJ exome AF: 0.000719

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0181

Gnomad NFE exome AF: 0.00950

Gnomad OTH exome AF: 0.00679

GnomAD4 exome AF: 0.00853 AC: 12433 AN: 1457816 Hom.: 99 Cov.: 30 AF XY: 0.00829 AC XY: 6010 AN XY: 724748

African (AFR) AF: 0.00380 AC: 127 AN: 33436

American (AMR) AF: 0.00268 AC: 119 AN: 44420

Ashkenazi Jewish (ASJ) AF: 0.000735 AC: 19 AN: 25848

East Asian (EAS) AF: 0.000177 AC: 7 AN: 39640

South Asian (SAS) AF: 0.000886 AC: 76 AN: 85794

European-Finnish (FIN) AF: 0.0170 AC: 907 AN: 53268

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5740

European-Non Finnish (NFE) AF: 0.00968 AC: 10743 AN: 1109486

Other (OTH) AF: 0.00701 AC: 422 AN: 60184

GnomAD4 genome AF: 0.00720 AC: 1096 AN: 152288 Hom.: 6 Cov.: 29 AF XY: 0.00773 AC XY: 576 AN XY: 74474

African (AFR) AF: 0.00496 AC: 206 AN: 41562

American (AMR) AF: 0.00457 AC: 70 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.0161 AC: 171 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00928 AC: 631 AN: 68016

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.171 Hom.: 6459

Bravo AF: 0.00597

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.00756 AC: 65

ExAC AF: 0.00707 AC: 858

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.00067	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.4
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.088
Sift	Benign	0.26	T
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.092
MVP		0.11
MPC		0.21
ClinPred		0.028	T
GERP RS		2.9
PromoterAI		-0.058	Neutral
Varity_R		0.21
gMVP		0.048
Mutation Taster		=296/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs143953255; hg19: chr1-155657901;