Genetic Variant ZFAT:p.Ala817Thr (chr8-134600462-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_020863.4(ZFAT):c.2449G>A(p.Ala817Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZFAT
NM_020863.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

Publications

0 publications found

Variant links:

Genes affected

ZFAT (HGNC:19899): (zinc finger and AT-hook domain containing) This gene encodes a protein that likely binds DNA and functions as a transcriptional regulator involved in apoptosis and cell survival. This gene resides in a susceptibility locus for autoimmune thyroid disease (AITD) on chromosome 8q24. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Nov 2009]

ZFAT links:

ZFAT-AS1 (HGNC:33992): (ZFAT antisense RNA 1) This gene encodes a small antisense RNA that may be involved in regulating the sense strand locus, zinc finger and AT hook domain containing. This RNA may play a role in B cell function. A single nucleotide polymorphism in the promoter of this gene is associated with an increased risk of autoimmune thyroid disease.[provided by RefSeq, Jan 2010]

ZFAT-AS1 links:

ENSG00000278454 (HGNC:):

ENSG00000278454 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=0.28352892).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020863.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFAT	NM_020863.4	MANE Select	c.2449G>A	p.Ala817Thr	missense	Exon 7 of 16	NP_065914.2
ZFAT	NM_001029939.4		c.2413G>A	p.Ala805Thr	missense	Exon 8 of 17	NP_001025110.2	Q9P243-2
ZFAT	NM_001167583.3		c.2413G>A	p.Ala805Thr	missense	Exon 7 of 16	NP_001161055.1	Q9P243-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFAT	ENST00000377838.8	TSL:1 MANE Select	c.2449G>A	p.Ala817Thr	missense	Exon 7 of 16	ENSP00000367069.3	Q9P243-1
ZFAT	ENST00000520214.5	TSL:1	c.2413G>A	p.Ala805Thr	missense	Exon 7 of 16	ENSP00000428483.1	Q9P243-2
ZFAT	ENST00000520727.5	TSL:1	c.2413G>A	p.Ala805Thr	missense	Exon 8 of 17	ENSP00000427831.1	Q9P243-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249580

AF XY:

0.00000739

show subpopulations

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:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0050

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

3.8

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.88

REVEL

Benign

0.089

Sift

Benign

0.26

Sift4G

Benign

0.43

Polyphen

0.63

Vest4

0.45

MutPred

0.38

Gain of methylation at K812 (P = 0.0454)

MVP

0.29

MPC

0.89

ClinPred

0.74

GERP RS

5.6

Varity_R

0.12

gMVP

0.37

Mutation Taster

=44/56

disease causing

(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