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GeneBe

8-134509637-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_020863.4(ZFAT):c.3474G>A(p.Thr1158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,613,360 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 67 hom., cov: 31)
Exomes 𝑓: 0.0018 ( 52 hom. )

Consequence

ZFAT
NM_020863.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.01
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-134509637-C-T is Benign according to our data. Variant chr8-134509637-C-T is described in ClinVar as [Benign]. Clinvar id is 778408.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.01 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZFATNM_020863.4 linkuse as main transcriptc.3474G>A p.Thr1158= synonymous_variant 15/16 ENST00000377838.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZFATENST00000377838.8 linkuse as main transcriptc.3474G>A p.Thr1158= synonymous_variant 15/161 NM_020863.4 P4Q9P243-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0154
AC:
2344
AN:
151950
Hom.:
67
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0534
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00504
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00293
Gnomad FIN
AF:
0.0000944
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00436
AC:
1086
AN:
248816
Hom.:
23
AF XY:
0.00353
AC XY:
476
AN XY:
134948
show subpopulations
Gnomad AFR exome
AF:
0.0569
Gnomad AMR exome
AF:
0.00235
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS exome
AF:
0.00284
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000257
Gnomad OTH exome
AF:
0.00132
GnomAD4 exome
AF:
0.00177
AC:
2591
AN:
1461294
Hom.:
52
Cov.:
30
AF XY:
0.00167
AC XY:
1215
AN XY:
726896
show subpopulations
Gnomad4 AFR exome
AF:
0.0544
Gnomad4 AMR exome
AF:
0.00291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000109
Gnomad4 OTH exome
AF:
0.00345
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0154
AC:
2342
AN:
152066
Hom.:
67
Cov.:
31
AF XY:
0.0149
AC XY:
1110
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.0532
Gnomad4 AMR
AF:
0.00504
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00272
Gnomad4 FIN
AF:
0.0000944
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00823
Hom.:
15
Bravo
AF:
0.0174
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
Cadd
Benign
0.14
Dann
Benign
0.66

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.

Other links and lift over

dbSNP: rs16905160; hg19: chr8-135521880; API