chr1-155659731-A-T

Position:

chr1-155659731-A-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting

The NM_139119.3(YY1AP1):c.2179T>A(p.Ser727Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000867 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

YY1AP1
NM_139119.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.426

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010348767).

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000381 (58/152268) while in subpopulation AMR AF= 0.00353 (54/15300). AF 95% confidence interval is 0.00278. There are 0 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YY1AP1	NM_139119.3 linkuse as main transcript	c.2179T>A	p.Ser727Thr	missense_variant	11/11	ENST00000355499.9	NP_620830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YY1AP1	ENST00000355499.9 linkuse as main transcript	c.2179T>A	p.Ser727Thr	missense_variant	11/11	1	NM_139119.3	ENSP00000347686	A2	Q9H869-2
	ENST00000500626.2 linkuse as main transcript	n.515T>A		non_coding_transcript_exon_variant	1/9

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000171

AC:

AN:

251454

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000809

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.0000703

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.0000561

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000381

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.000344

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.2593T>A (p.S865T) alteration is located in exon 10 (coding exon 10) of the YY1AP1 gene. This alteration results from a T to A substitution at nucleotide position 2593, causing the serine (S) at amino acid position 865 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.055

DANN

Benign

0.68

DEOGEN2

Benign

0.0033

.;.;.;.;.;.;.;.;.;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.031

T;.;T;.;.;.;T;T;T;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.010

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

.;.;.;.;.;.;.;.;.;L;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N;N;N;N;N

PROVEAN

Benign

-0.30

N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.011

Sift

Benign

0.79

.;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.45

T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0

.;.;.;B;.;B;B;.;.;B;B

Vest4

0.10

MutPred

0.22

.;.;.;.;.;.;.;.;.;Gain of loop (P = 3e-04);.;

MVP

0.072

MPC

0.13

ClinPred

0.014

GERP RS

-4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.076

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