Genetic Variant ZNF639:c.*3925A>G (chr3-179338347-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001303426.2(ZNF639):c.*3925A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,144 control chromosomes in the GnomAD database, including 2,336 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 0.17 ( 2336 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF639
NM_001303426.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.957

Publications

7 publications found

Variant links:

Genes affected

ZNF639 (HGNC:30950): (zinc finger protein 639) This gene encodes a member of the Kruppel-like zinc finger family of proteins. Amplification and overexpression of this gene have been observed in esophageal squamous cell carcinoma. The encoded protein has been shown to bind DNA in a sequence-specific manner and may regulate HIV-1 gene expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ZNF639 links:

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new If you want to explore the variant's impact on the transcript NM_001303426.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.52).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303426.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF639	NM_001303426.2	MANE Select	c.*3925A>G	3_prime_UTR	Exon 6 of 6	NP_001290355.1	Q9UID6
ZNF639	NM_001303425.2		c.*3925A>G	3_prime_UTR	Exon 7 of 7	NP_001290354.1	Q9UID6
ZNF639	NM_001375800.1		c.*3925A>G	3_prime_UTR	Exon 7 of 7	NP_001362729.1	Q9UID6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF639	ENST00000496856.6	TSL:1 MANE Select	c.*3925A>G		3_prime_UTR	Exon 6 of 6	ENSP00000417740.1	Q9UID6
	ZNF639	ENST00000326361.7	TSL:1	c.*3925A>G		3_prime_UTR	Exon 7 of 7	ENSP00000325634.3	Q9UID6

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

26036

AN:

152026

Hom.:

2335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.192

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.171

AC:

26043

AN:

152144

Hom.:

2336

Cov.:

AF XY:

0.174

AC XY:

12966

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.131

AC:

5437

AN:

41500

American (AMR)

AF:

0.235

AC:

3588

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

671

AN:

3466

East Asian (EAS)

AF:

0.217

AC:

1122

AN:

5174

South Asian (SAS)

AF:

0.194

AC:

938

AN:

4830

European-Finnish (FIN)

AF:

0.151

AC:

1597

AN:

10580

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.177

AC:

12054

AN:

67996

Other (OTH)

AF:

0.191

AC:

402

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1128

2256

3384

4512

5640

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<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:

0.182

Hom.:

4216

Bravo

AF:

0.179

Asia WGS

AF:

0.225

AC:

783

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.8

(source)

DANN

Benign

0.91

PhyloP100

0.96

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over