chr12-42235748-T-A

Variant names:

• chr12-42235748-T-A
• rs7960176
• NM_005748.6:c.152+1851A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001190980.3(YAF2):​c.*48A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: YAF2 NM_001190980.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 13 publications found

Genes affected

YAF2 (HGNC:17363): (YY1 associated factor 2) This gene encodes a zinc finger containing protein that functions in the regulation of transcription. This protein was identified as an interacting partner of transcriptional repressor protein Yy1, and also interacts with other transcriptional regulators, including Myc and Polycomb. This protein can promote proteolysis of Yy1. Multiple alternatively spliced transcript variants have been found. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190980.3. 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
	YAF2	NM_005748.6	MANE Select	c.152+1851A>T		intron	N/A	NP_005739.2	Q8IY57-1
	YAF2	NM_001190980.3		c.*48A>T		3_prime_UTR	Exon 3 of 3	NP_001177909.1	Q8IY57-4
	YAF2	NM_001190979.3		c.152+1851A>T		intron	N/A	NP_001177908.1	Q8IY57-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YAF2	ENST00000534854.7	TSL:1 MANE Select	c.152+1851A>T		intron	N/A	ENSP00000439256.2	Q8IY57-1
	YAF2	ENST00000327791.8	TSL:1	c.152+1851A>T		intron	N/A	ENSP00000328004.5	Q8IY57-5
	YAF2	ENST00000555248.2	TSL:2	c.*48A>T		3_prime_UTR	Exon 3 of 3	ENSP00000451626.2	Q8IY57-4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.23e-7 AC: 1 AN: 1383032 Hom.: 0 Cov.: 53 AF XY: 0.00000147 AC XY: 1 AN XY: 682466

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

African (AFR) AF: 0.00 AC: 0 AN: 31548

American (AMR) AF: 0.00 AC: 0 AN: 35674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5380

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078772

Other (OTH) AF: 0.00 AC: 0 AN: 57828

⚠️ 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 Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Uncertain	0.99
PhyloP100		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs7960176; hg19: chr12-42629550;