1-155688110-A-G

Variant summary

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

The ENST00000355499.9(YY1AP1):​c.-60T>C variant causes a 5 prime UTR 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. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 6 hom., cov: 29)
Exomes 𝑓: 0.0085 ( 99 hom. )

Consequence

YY1AP1
ENST00000355499.9 5_prime_UTR

Scores

17

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.40
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]
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]

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=0.0037935078).
BP6
Variant 1-155688110-A-G is Benign according to our data. Variant chr1-155688110-A-G is described in ClinVar as [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
YY1AP1NM_139119.3 linkuse as main transcriptc.-60T>C 5_prime_UTR_variant 2/11 ENST00000355499.9 NP_620830.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
YY1AP1ENST00000355499.9 linkuse as main transcriptc.-60T>C 5_prime_UTR_variant 2/111 NM_139119.3 ENSP00000347686 A2Q9H869-2

Frequencies

GnomAD3 genomes
AF:
0.00722
AC:
1098
AN:
152170
Hom.:
6
Cov.:
29
show subpopulations
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
GnomAD3 exomes
AF:
0.00684
AC:
1699
AN:
248404
Hom.:
12
AF XY:
0.00678
AC XY:
912
AN XY:
134596
show subpopulations
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 SAS exome
AF:
0.000730
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
show subpopulations
Gnomad4 AFR exome
AF:
0.00380
Gnomad4 AMR exome
AF:
0.00268
Gnomad4 ASJ exome
AF:
0.000735
Gnomad4 EAS exome
AF:
0.000177
Gnomad4 SAS exome
AF:
0.000886
Gnomad4 FIN exome
AF:
0.0170
Gnomad4 NFE exome
AF:
0.00968
Gnomad4 OTH exome
AF:
0.00701
GnomAD4 genome
AF:
0.00720
AC:
1096
AN:
152288
Hom.:
6
Cov.:
29
AF XY:
0.00773
AC XY:
576
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.00496
Gnomad4 AMR
AF:
0.00457
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000830
Gnomad4 FIN
AF:
0.0161
Gnomad4 NFE
AF:
0.00928
Gnomad4 OTH
AF:
0.00425
Alfa
AF:
0.00817
Hom.:
3
Bravo
AF:
0.00597
ESP6500AA
AF:
0.00227
AC:
10
ESP6500EA
AF:
0.00756
AC:
65
ExAC
AF:
0.00707
AC:
858

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2024YY1AP1: BP4, BS2 -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 08, 2018- -

Computational scores

Source: dbNSFP v4.3

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;T;T;T
MetaRNN
Benign
0.0038
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;.;N;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D;N;N;N;N
PROVEAN
Benign
-0.42
N;N;N;N
REVEL
Benign
0.088
Sift
Benign
0.26
.;T;T;T
Sift4G
Benign
0.15
T;T;T;T
Polyphen
0.0
.;.;B;B
Vest4
0.092
MVP
0.11
MPC
0.21
ClinPred
0.028
T
GERP RS
2.9
Varity_R
0.21
gMVP
0.048

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs143953255; hg19: chr1-155657901; API