12-42238158-G-A

Variant names:

• chr12-42238158-G-A
• rs979370843
• NM_005748.6:c.23C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005748.6(YAF2):​c.23C>T​(p.Thr8Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000175 in 1,546,830 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: YAF2 NM_005748.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.74
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20711887).
• BS2: High AC in GnomAdExome4 at 24 AD gene.

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.23C>T	p.Thr8Ile	missense	Exon 1 of 4	NP_005739.2	Q8IY57-1
	YAF2	NM_001190979.3		c.23C>T	p.Thr8Ile	missense	Exon 1 of 5	NP_001177908.1	Q8IY57-5
	YAF2	NM_001190977.3		c.23C>T	p.Thr8Ile	missense	Exon 1 of 3	NP_001177906.1	Q8IY57-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YAF2	ENST00000534854.7	TSL:1 MANE Select	c.23C>T	p.Thr8Ile	missense	Exon 1 of 4	ENSP00000439256.2	Q8IY57-1
	YAF2	ENST00000327791.8	TSL:1	c.23C>T	p.Thr8Ile	missense	Exon 1 of 5	ENSP00000328004.5	Q8IY57-5
	YAF2	ENST00000880607.1		c.23C>T	p.Thr8Ile	missense	Exon 1 of 4	ENSP00000550666.1

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 150610 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000296

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000110 AC: 2 AN: 181362 AF XY: 0.00000986

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000253

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000172 AC: 24 AN: 1396220 Hom.: 0 Cov.: 31 AF XY: 0.0000130 AC XY: 9 AN XY: 693722

African (AFR) AF: 0.00 AC: 0 AN: 28774

American (AMR) AF: 0.00 AC: 0 AN: 37848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24262

East Asian (EAS) AF: 0.00 AC: 0 AN: 32710

South Asian (SAS) AF: 0.00 AC: 0 AN: 79838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4724

European-Non Finnish (NFE) AF: 0.0000222 AC: 24 AN: 1080664

Other (OTH) AF: 0.00 AC: 0 AN: 57032

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 150610 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 73530

African (AFR) AF: 0.0000243 AC: 1 AN: 41126

American (AMR) AF: 0.00 AC: 0 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5076

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67484

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.0000583 Hom.: 0

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	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.033
Eigen_PC	Benign	-0.052
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.60	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.7
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.18
Sift	Benign	0.11	T
Sift4G	Benign	0.18	T
Polyphen		0.93	P
Vest4		0.42
MVP		0.043
ClinPred		0.60	D
GERP RS		3.0
PromoterAI		0.080	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.63
Mutation Taster		=40/60	disease causing

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: rs979370843; hg19: chr12-42631960;