chr1-155688145-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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. 12/19 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.422

Variant links:

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]

YY1AP1 links:

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]

DAP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YY1AP1	NM_139119.3 link	c.-95G>A		5_prime_UTR_variant	Exon 2 of 11	ENST00000355499.9	NP_620830.1	Q9H869-2I6L9C2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YY1AP1	ENST00000355499.9 link	c.-95G>A		5_prime_UTR_variant	Exon 2 of 11	1	NM_139119.3	ENSP00000347686.4		Q9H869-2

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1542

AN:

152222

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00928

AC:

2316

AN:

249446

Hom.:

AF XY:

0.00924

AC XY:

1252

AN XY:

135496

show subpopulations

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 SAS exome

AF:

0.00199

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.:

AF XY:

0.0159

AC XY:

11554

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.00296

Gnomad4 AMR exome

AF:

0.00595

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00181

Gnomad4 FIN exome

AF:

0.00640

Gnomad4 NFE exome

AF:

0.0204

Gnomad4 OTH exome

AF:

0.0147

GnomAD4 genome

AF:

0.0101

AC:

1541

AN:

152340

Hom.:

Cov.:

AF XY:

0.00890

AC XY:

663

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00402

Gnomad4 AMR

AF:

0.00895

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00593

Gnomad4 NFE

AF:

0.0168

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.0105

TwinsUK

AF:

0.0135

AC:

ALSPAC

AF:

0.0208

AC:

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.0166

AC:

143

ExAC

AF:

0.00913

AC:

1108

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0156

EpiControl

AF:

0.0142

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0013

.;.;T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.53

T;T;T;T

MetaRNN

Benign

0.0052

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;.;N;.

PROVEAN

Benign

2.6

N;N;N;N

REVEL

Benign

0.069

Sift

Pathogenic

0.0

.;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.031

.;.;B;B

Vest4

0.14

MVP

0.16

MPC

0.44

ClinPred

0.086

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.045

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over