Genetic Variant YAF2:p.Ala34Thr (chr12-42237651-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005748.6(YAF2):c.100G>A(p.Ala34Thr) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A34P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

YAF2
NM_005748.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.38

Publications

2 publications found

Variant links:

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]

YAF2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35915744).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YAF2	NM_005748.6	MANE Select	c.100G>A	p.Ala34Thr	missense	Exon 2 of 4	NP_005739.2	Q8IY57-1
YAF2	NM_001190979.3		c.100G>A	p.Ala34Thr	missense	Exon 2 of 5	NP_001177908.1	Q8IY57-5
YAF2	NM_001190980.3		c.100G>A	p.Ala34Thr	missense	Exon 2 of 3	NP_001177909.1	Q8IY57-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YAF2	ENST00000534854.7	TSL:1 MANE Select	c.100G>A	p.Ala34Thr	missense	Exon 2 of 4	ENSP00000439256.2	Q8IY57-1
YAF2	ENST00000327791.8	TSL:1	c.100G>A	p.Ala34Thr	missense	Exon 2 of 5	ENSP00000328004.5	Q8IY57-5
YAF2	ENST00000555248.2	TSL:2	c.100G>A	p.Ala34Thr	missense	Exon 2 of 3	ENSP00000451626.2	Q8IY57-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

202930

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1429518

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708646

African (AFR)

AF:

0.00

AC:

AN:

32002

American (AMR)

AF:

0.00

AC:

AN:

40694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25438

East Asian (EAS)

AF:

0.00

AC:

AN:

37270

South Asian (SAS)

AF:

0.00

AC:

AN:

81034

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50830

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097354

Other (OTH)

AF:

0.00

AC:

AN:

59178

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.36

MetaSVM

Uncertain

-0.28

MutationAssessor

Uncertain

2.5

PhyloP100

4.4

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.26

Sift

Benign

0.16

Sift4G

Uncertain

0.054

Polyphen

0.67

Vest4

0.39

MutPred

0.62

Gain of relative solvent accessibility (P = 0.0215)

MVP

0.11

ClinPred

0.99

GERP RS

4.2

PromoterAI

-0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.64

gMVP

0.73

Mutation Taster

=158/142

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over