12-42237690-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YAF2	NM_005748.6	c.61G>A	p.Gly21Ser	missense_variant	Exon 2 of 4	ENST00000534854.7	NP_005739.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YAF2	ENST00000534854.7	c.61G>A	p.Gly21Ser	missense_variant	Exon 2 of 4	1	NM_005748.6	ENSP00000439256.2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.13e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 11, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.61G>A (p.G21S) alteration is located in exon 2 (coding exon 2) of the YAF2 gene. This alteration results from a G to A substitution at nucleotide position 61, causing the glycine (G) at amino acid position 21 to be replaced by a serine (S). 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	0.29
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;D;D
M_CAP	Pathogenic	0.54	D
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Uncertain	0.0016	D
MutationAssessor	Uncertain	2.2	M;M;M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Uncertain	0.41
Sift	Benign	0.042	D;T;D
Sift4G	Benign	0.086	T;T;T
Polyphen		0.96	.;D;.
Vest4		0.53
MutPred		0.49		Gain of phosphorylation at G21 (P = 0.0183);Gain of phosphorylation at G21 (P = 0.0183);Gain of phosphorylation at G21 (P = 0.0183);
MVP		0.19
ClinPred		0.99	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.62
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-42631492;