Genetic Variant NM_025112.5:c.1140-51T>C (chr3-126471076-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_025112.5(ZXDC):c.1140-51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,586,982 control chromosomes in the GnomAD database, including 360,225 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 0.61 ( 28945 hom., cov: 33)

Exomes 𝑓: 0.68 ( 331280 hom. )

Consequence

ZXDC
NM_025112.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.649

Publications

13 publications found

Variant links:

Genes affected

ZXDC (HGNC:28160): (ZXD family zinc finger C) Enables C2H2 zinc finger domain binding activity; LRR domain binding activity; and transcription coactivator activity. Involved in positive regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZXDC 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=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025112.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZXDC	NM_025112.5	MANE Select	c.1140-51T>C	intron	N/A	NP_079388.3
ZXDC	NM_001040653.4		c.1140-51T>C	intron	N/A	NP_001035743.1	Q2QGD7-2
ZXDC	NR_104249.2		n.1166-51T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZXDC	ENST00000389709.8	TSL:1 MANE Select	c.1140-51T>C	intron	N/A	ENSP00000374359.3	Q2QGD7-1
ZXDC	ENST00000336332.5	TSL:1	c.1140-51T>C	intron	N/A	ENSP00000337694.5	Q2QGD7-2
ZXDC	ENST00000515545.5	TSL:1	n.261-51T>C	intron	N/A	ENSP00000426532.1	H0YAA9

Frequencies

GnomAD3 genomes

AF:

0.611

AC:

92885

AN:

152028

Hom.:

28922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.796

Gnomad AMR

AF:

0.618

Gnomad ASJ

AF:

0.629

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.742

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.676

Gnomad OTH

AF:

0.622

GnomAD2 exomes

AF:

0.653

AC:

151149

AN:

231500

AF XY:

0.666

show subpopulations

Gnomad AFR exome

AF:

0.483

Gnomad AMR exome

AF:

0.586

Gnomad ASJ exome

AF:

0.642

Gnomad EAS exome

AF:

0.574

Gnomad FIN exome

AF:

0.653

Gnomad NFE exome

AF:

0.681

Gnomad OTH exome

AF:

0.647

GnomAD4 exome

AF:

0.678

AC:

972377

AN:

1434836

Hom.:

331280

Cov.:

AF XY:

0.682

AC XY:

484409

AN XY:

710390

show subpopulations

African (AFR)

AF:

0.470

AC:

15243

AN:

32432

American (AMR)

AF:

0.590

AC:

24312

AN:

41218

Ashkenazi Jewish (ASJ)

AF:

0.643

AC:

16392

AN:

25488

East Asian (EAS)

AF:

0.535

AC:

20898

AN:

39072

South Asian (SAS)

AF:

0.756

AC:

64124

AN:

84788

European-Finnish (FIN)

AF:

0.650

AC:

34349

AN:

52840

Middle Eastern (MID)

AF:

0.664

AC:

3772

AN:

5684

European-Non Finnish (NFE)

AF:

0.689

AC:

754063

AN:

1094188

Other (OTH)

AF:

0.663

AC:

39224

AN:

59126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

15635

31269

46904

62538

78173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19436

38872

58308

77744

97180

<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:

0.611

AC:

92944

AN:

152146

Hom.:

28945

Cov.:

AF XY:

0.611

AC XY:

45425

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.476

AC:

19728

AN:

41488

American (AMR)

AF:

0.618

AC:

9448

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.629

AC:

2183

AN:

3472

East Asian (EAS)

AF:

0.558

AC:

2886

AN:

5174

South Asian (SAS)

AF:

0.743

AC:

3585

AN:

4824

European-Finnish (FIN)

AF:

0.652

AC:

6905

AN:

10598

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.676

AC:

45968

AN:

67990

Other (OTH)

AF:

0.623

AC:

1314

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1838

3676

5513

7351

9189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.661

Hom.:

18930

Bravo

AF:

0.601

Asia WGS

AF:

0.611

AC:

2127

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.7

(source)

DANN

Benign

0.43

PhyloP100

-0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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