rs397834368

Variant names:

• chr1-155660137-G-A
• rs397834368
• NM_139119.3:c.1773C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_139119.3(YY1AP1):​c.1773C>T​(p.Ala591Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000571 in 1,613,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00057 (0 hom.)
• Consequence: YY1AP1 NM_139119.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.172
• Publications: 0 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]

YY1AP1 Gene-Disease associations (from GenCC):

• grange syndrome

  Inheritance: AR, AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 1-155660137-G-A is Benign according to our data. Variant chr1-155660137-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 709137.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.172 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139119.3. 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.1773C>T	p.Ala591Ala	synonymous	Exon 11 of 11	NP_620830.1	Q9H869-2
	YY1AP1	NM_001198903.1		c.2187C>T	p.Ala729Ala	synonymous	Exon 10 of 10	NP_001185832.1	Q9H869-9
	YY1AP1	NM_001198904.1		c.2127C>T	p.Ala709Ala	synonymous	Exon 10 of 10	NP_001185833.1	Q9H869-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YY1AP1	ENST00000355499.9	TSL:1 MANE Select	c.1773C>T	p.Ala591Ala	synonymous	Exon 11 of 11	ENSP00000347686.4	Q9H869-2
	YY1AP1	ENST00000368340.10	TSL:1	c.2127C>T	p.Ala709Ala	synonymous	Exon 10 of 10	ENSP00000357324.5	Q9H869-8
	YY1AP1	ENST00000347088.9	TSL:1	c.1773C>T	p.Ala591Ala	synonymous	Exon 10 of 10	ENSP00000316079.6	Q9H869-2

Frequencies

GnomAD3 genomes AF: 0.000558 AC: 85 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000119 AC: 30 AN: 251328 AF XY: 0.000118

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000572 AC: 836 AN: 1460802 Hom.: 0 Cov.: 31 AF XY: 0.000528 AC XY: 384 AN XY: 726736

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000179 AC: 6 AN: 33476

American (AMR) AF: 0.000157 AC: 7 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86240

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000707 AC: 785 AN: 1110958

Other (OTH) AF: 0.000381 AC: 23 AN: 60384

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000558 AC: 85 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.000456 AC XY: 34 AN XY: 74492

African (AFR) AF: 0.000192 AC: 8 AN: 41564

American (AMR) AF: 0.000196 AC: 3 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00104 AC: 71 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000424 Hom.: 0

Bravo AF: 0.000533

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	YY1AP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.86
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs397834368; hg19: chr1-155629928; COSMIC: COSV55124789; COSMIC: COSV55124789;