Genetic Variant ZFAT:c.634+73A>G (chr8-134610397-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020863.4(ZFAT):c.634+73A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,481,682 control chromosomes in the GnomAD database, including 125,932 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 12637 hom., cov: 32)

Exomes 𝑓: 0.41 ( 113295 hom. )

Consequence

ZFAT
NM_020863.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0810

Publications

6 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
ZFAT	NM_020863.4	MANE Select	c.634+73A>G	intron	N/A	NP_065914.2
ZFAT	NM_001029939.4		c.598+73A>G	intron	N/A	NP_001025110.2	Q9P243-2
ZFAT	NM_001167583.3		c.598+73A>G	intron	N/A	NP_001161055.1	Q9P243-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZFAT	ENST00000377838.8	TSL:1 MANE Select	c.634+73A>G	intron	N/A	ENSP00000367069.3	Q9P243-1
ZFAT	ENST00000520214.5	TSL:1	c.598+73A>G	intron	N/A	ENSP00000428483.1	Q9P243-2
ZFAT	ENST00000520727.5	TSL:1	c.598+73A>G	intron	N/A	ENSP00000427831.1	Q9P243-2

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60458

AN:

151968

Hom.:

12622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.304

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.543

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.537

Gnomad SAS

AF:

0.519

Gnomad FIN

AF:

0.520

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.397

GnomAD4 exome

AF:

0.409

AC:

543582

AN:

1329596

Hom.:

113295

AF XY:

0.410

AC XY:

268702

AN XY:

655144

show subpopulations

African (AFR)

AF:

0.299

AC:

8811

AN:

29470

American (AMR)

AF:

0.611

AC:

16395

AN:

26846

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

6913

AN:

20566

East Asian (EAS)

AF:

0.537

AC:

20461

AN:

38112

South Asian (SAS)

AF:

0.496

AC:

34222

AN:

68984

European-Finnish (FIN)

AF:

0.498

AC:

24511

AN:

49210

Middle Eastern (MID)

AF:

0.328

AC:

1699

AN:

5176

European-Non Finnish (NFE)

AF:

0.394

AC:

408100

AN:

1036128

Other (OTH)

AF:

0.408

AC:

22470

AN:

55104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

15430

30860

46290

61720

77150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13106

26212

39318

52424

65530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.398

AC:

60502

AN:

152086

Hom.:

12637

Cov.:

AF XY:

0.408

AC XY:

30346

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.304

AC:

12620

AN:

41516

American (AMR)

AF:

0.543

AC:

8308

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

1124

AN:

3470

East Asian (EAS)

AF:

0.537

AC:

2769

AN:

5152

South Asian (SAS)

AF:

0.519

AC:

2500

AN:

4818

European-Finnish (FIN)

AF:

0.520

AC:

5501

AN:

10578

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.389

AC:

26434

AN:

67948

Other (OTH)

AF:

0.400

AC:

845

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1845

3690

5536

7381

9226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.289

Hom.:

959

Bravo

AF:

0.394

Asia WGS

AF:

0.523

AC:

1818

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.2

(source)

DANN

Benign

0.67

PhyloP100

-0.081

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over