chr12-42237690-C-T

Variant names:

• chr12-42237690-C-T
• NM_005748.6:c.61G>A

Variant summary

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

The NM_005748.6(YAF2):​c.61G>A​(p.Gly21Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000703 in 1,423,242 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: YAF2 NM_005748.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005748.6. 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.61G>A	p.Gly21Ser	missense	Exon 2 of 4	NP_005739.2	Q8IY57-1
	YAF2	NM_001190979.3		c.61G>A	p.Gly21Ser	missense	Exon 2 of 5	NP_001177908.1	Q8IY57-5
	YAF2	NM_001190980.3		c.61G>A	p.Gly21Ser	missense	Exon 2 of 3	NP_001177909.1	Q8IY57-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YAF2	ENST00000534854.7	TSL:1 MANE Select	c.61G>A	p.Gly21Ser	missense	Exon 2 of 4	ENSP00000439256.2	Q8IY57-1
	YAF2	ENST00000327791.8	TSL:1	c.61G>A	p.Gly21Ser	missense	Exon 2 of 5	ENSP00000328004.5	Q8IY57-5
	YAF2	ENST00000555248.2	TSL:2	c.61G>A	p.Gly21Ser	missense	Exon 2 of 3	ENSP00000451626.2	Q8IY57-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1423242 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 707026

African (AFR) AF: 0.00 AC: 0 AN: 30344

American (AMR) AF: 0.00 AC: 0 AN: 39990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25198

East Asian (EAS) AF: 0.00 AC: 0 AN: 35032

South Asian (SAS) AF: 0.00 AC: 0 AN: 81586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095372

Other (OTH) AF: 0.00 AC: 0 AN: 58710

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3474

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.54	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Uncertain	0.0016	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.1
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.41
Sift	Benign	0.042	D
Sift4G	Benign	0.086	T
Polyphen		0.96	D
Vest4		0.53
MutPred		0.49		Gain of phosphorylation at G21 (P = 0.0183)
MVP		0.19
ClinPred		0.99	D
GERP RS		4.1
PromoterAI		-0.043	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.62
gMVP		0.64
Mutation Taster		=169/131	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

hg19: chr12-42631492;