Variant 8-134478659-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000429442.6(ZFAT):c.3409G>A(p.Val1137Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000501 in 1,583,022 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 4 hom. )

Consequence

ZFAT
ENST00000429442.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.28

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034586787).

BP6

Variant 8-134478659-C-T is Benign according to our data. Variant chr8-134478659-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 713509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAT	NM_020863.4 linkuse as main transcript	c.3555G>A	p.Ala1185=	synonymous_variant	16/16	ENST00000377838.8	NP_065914.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFAT	ENST00000377838.8 linkuse as main transcript	c.3555G>A	p.Ala1185=	synonymous_variant	16/16	1	NM_020863.4	ENSP00000367069	P4	Q9P243-1

Frequencies

GnomAD3 genomes

AF:

0.00180

AC:

274

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00591

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000472

AC:

AN:

199060

Hom.:

AF XY:

0.000383

AC XY:

AN XY:

107080

show subpopulations

Gnomad AFR exome

AF:

0.00590

Gnomad AMR exome

AF:

0.000372

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000401

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000161

Gnomad OTH exome

AF:

0.000586

GnomAD4 exome

AF:

0.000361

AC:

517

AN:

1430704

Hom.:

Cov.:

AF XY:

0.000370

AC XY:

262

AN XY:

708592

show subpopulations

Gnomad4 AFR exome

AF:

0.00599

Gnomad4 AMR exome

AF:

0.000345

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000215

Gnomad4 OTH exome

AF:

0.000844

GnomAD4 genome

AF:

0.00181

AC:

276

AN:

152318

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

108

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00594

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00115

Hom.:

Bravo

AF:

0.00176

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00459

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.000475

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 18, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2022	ZFAT: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D;D;N

PROVEAN

Benign

-0.20

REVEL

Benign

0.050

Sift

Uncertain

0.024

Sift4G

Benign

0.21

Vest4

0.014

MVP

0.061

ClinPred

0.0091

GERP RS

-1.8

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over