chr1-155688224-G-A

Position:

chr1-155688224-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_001198903.1(YY1AP1):c.241C>T(p.Leu81Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,613,416 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

YY1AP1
NM_001198903.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 3.50

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:

LOC124904430 (HGNC:):

LOC124904430 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0077566803).

BP6

Variant 1-155688224-G-A is Benign according to our data. Variant chr1-155688224-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 720286.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0016 (243/152338) while in subpopulation AFR AF= 0.00568 (236/41584). AF 95% confidence interval is 0.00508. There are 0 homozygotes in gnomad4. There are 125 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YY1AP1	NM_139119.3 linkuse as main transcript	c.-151-23C>T		intron_variant		ENST00000355499.9	NP_620830.1	Q9H869-2I6L9C2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YY1AP1	ENST00000355499.9 linkuse as main transcript	c.-151-23C>T		intron_variant		1	NM_139119.3	ENSP00000347686.4		Q9H869-2

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

244

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00572

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000411

AC:

101

AN:

245482

Hom.:

AF XY:

0.000291

AC XY:

AN XY:

134120

show subpopulations

Gnomad AFR exome

AF:

0.00657

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000173

AC:

253

AN:

1461078

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

726804

show subpopulations

Gnomad4 AFR exome

AF:

0.00666

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.00160

AC:

243

AN:

152338

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00568

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000370

Hom.:

Bravo

AF:

0.00197

ESP6500AA

AF:

0.00502

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000561

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2024

The c.241C>T (p.L81F) alteration is located in exon 1 (coding exon 1) of the YY1AP1 gene. This alteration results from a C to T substitution at nucleotide position 241, causing the leucine (L) at amino acid position 81 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

YY1AP1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.14

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.34

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.0078

T;T;T

MetaSVM

Benign

-1.1

PROVEAN

Benign

-0.83

N;N;N

REVEL

Benign

0.095

Sift

Pathogenic

0.0

.;D;D

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

1.0

.;.;D

Vest4

0.31

MVP

0.30

MPC

0.18

ClinPred

0.24

GERP RS

2.6

gMVP

0.077

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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