Variant 8-134478707-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020863.4(ZFAT):c.3507G>C(p.Glu1169Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,415,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1169A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZFAT
NM_020863.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19480282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFAT	NM_020863.4 linkuse as main transcript	c.3507G>C	p.Glu1169Asp	missense_variant	16/16	ENST00000377838.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFAT	ENST00000377838.8 linkuse as main transcript	c.3507G>C	p.Glu1169Asp	missense_variant	16/16	1	NM_020863.4	P4	Q9P243-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1415972

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

699746

show subpopulations

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:

0.00000184

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.3507G>C (p.E1169D) alteration is located in exon 16 (coding exon 16) of the ZFAT gene. This alteration results from a G to C substitution at nucleotide position 3507, causing the glutamic acid (E) at amino acid position 1169 to be replaced by an aspartic acid (D). 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

0.15

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0088

T;.;T;.;.;.

Eigen

Benign

0.078

Eigen_PC

Benign

0.064

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.92

D;.;D;D;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.19

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.75

D;D;D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.44

N;N;N;N;D;N

REVEL

Benign

0.068

Sift

Uncertain

0.023

D;D;D;D;D;D

Sift4G

Benign

0.063

T;T;T;T;D;T

Polyphen

0.99

D;.;D;.;.;.

Vest4

0.40

MutPred

0.35

.;.;Loss of loop (P = 0.0512);.;.;.;

MVP

0.31

MPC

0.79

ClinPred

0.72

GERP RS

1.9

Varity_R

0.077

gMVP

0.30

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over