dbSNP rs758643167: 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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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