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GeneBe

8-134520970-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_020863.4(ZFAT):c.3147A>G(p.Val1049=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00184 in 1,613,792 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0099 ( 20 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 28 hom. )

Consequence

ZFAT
NM_020863.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.21
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=-0.89).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-134520970-T-C is Benign according to our data. Variant chr8-134520970-T-C is described in ClinVar as [Benign]. Clinvar id is 780780.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=-4.21 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00991 (1508/152208) while in subpopulation AFR AF= 0.0346 (1438/41512). AF 95% confidence interval is 0.0332. There are 20 homozygotes in gnomad4. There are 706 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 20 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZFATNM_020863.4 linkuse as main transcriptc.3147A>G p.Val1049= synonymous_variant 13/16 ENST00000377838.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZFATENST00000377838.8 linkuse as main transcriptc.3147A>G p.Val1049= synonymous_variant 13/161 NM_020863.4 P4Q9P243-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00992
AC:
1509
AN:
152090
Hom.:
20
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0348
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00275
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00910
GnomAD3 exomes
AF:
0.00249
AC:
620
AN:
249150
Hom.:
12
AF XY:
0.00173
AC XY:
234
AN XY:
135172
show subpopulations
Gnomad AFR exome
AF:
0.0348
Gnomad AMR exome
AF:
0.00174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000142
Gnomad OTH exome
AF:
0.000826
GnomAD4 exome
AF:
0.00100
AC:
1462
AN:
1461584
Hom.:
28
Cov.:
30
AF XY:
0.000806
AC XY:
586
AN XY:
727066
show subpopulations
Gnomad4 AFR exome
AF:
0.0343
Gnomad4 AMR exome
AF:
0.00197
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000836
Gnomad4 OTH exome
AF:
0.00204
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00991
AC:
1508
AN:
152208
Hom.:
20
Cov.:
32
AF XY:
0.00949
AC XY:
706
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.0346
Gnomad4 AMR
AF:
0.00274
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00900
Alfa
AF:
0.00413
Hom.:
5
Bravo
AF:
0.0111
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000545
EpiControl
AF:
0.000237

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
-0.89
Cadd
Benign
0.39
Dann
Benign
0.65

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: rs114589731; hg19: chr8-135533213; API