Genetic Variant YAF2:p.Ala34Ser (chr12-42237651-C-A) – 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>T(p.Ala34Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000021 in 1,429,516 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000021 ( 0 hom. )

Consequence

YAF2
NM_005748.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.38

Publications

0 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=0.35554996).

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>T	p.Ala34Ser	missense	Exon 2 of 4	NP_005739.2	Q8IY57-1
YAF2	NM_001190979.3		c.100G>T	p.Ala34Ser	missense	Exon 2 of 5	NP_001177908.1	Q8IY57-5
YAF2	NM_001190980.3		c.100G>T	p.Ala34Ser	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>T	p.Ala34Ser	missense	Exon 2 of 4	ENSP00000439256.2	Q8IY57-1
YAF2	ENST00000327791.8	TSL:1	c.100G>T	p.Ala34Ser	missense	Exon 2 of 5	ENSP00000328004.5	Q8IY57-5
YAF2	ENST00000555248.2	TSL:2	c.100G>T	p.Ala34Ser	missense	Exon 2 of 3	ENSP00000451626.2	Q8IY57-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1429516

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

708644

show subpopulations

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:

0.00000273

AC:

AN:

1097352

Other (OTH)

AF:

0.00

AC:

AN:

59178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.8

PhyloP100

4.4

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.3

REVEL

Benign

0.23

Sift

Benign

0.18

Sift4G

Benign

0.15

Polyphen

0.48

Vest4

0.46

MutPred

0.62

Gain of relative solvent accessibility (P = 0.0082)

MVP

0.082

ClinPred

0.98

GERP RS

4.2

PromoterAI

-0.057

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.48

gMVP

0.64

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over