Genetic Variant ZNF331:c.-410A>G (chr19-53521947-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 ENST00000253144.13(ZNF331):c.-410A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 151,930 control chromosomes in the GnomAD database, including 30,930 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 0.63 ( 30918 hom., cov: 31)

Exomes 𝑓: 0.70 ( 12 hom. )

Consequence

ZNF331
ENST00000253144.13 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.930

Publications

8 publications found

Variant links:

Genes affected

ZNF331 (HGNC:15489): (zinc finger protein 331) This gene encodes a zinc finger protein containing a KRAB (Kruppel-associated box) domain found in transcriptional repressors. This gene may be methylated and silenced in cancer cells. This gene is located within a differentially methylated region (DMR) and shows allele-specific expression in placenta. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding the same protein. [provided by RefSeq, Nov 2015]

ZNF331 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 (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000253144.13. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
ZNF331	NM_001317120.2	c.-372A>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_001304049.1
ZNF331	NM_018555.6	c.-410A>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_061025.5
ZNF331	NM_001317120.2	c.-372A>G	5_prime_UTR	Exon 1 of 7	NP_001304049.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZNF331	ENST00000253144.13	TSL:1	c.-410A>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000253144.9
ZNF331	ENST00000502248.5	TSL:1	c.-372A>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000423675.1
ZNF331	ENST00000253144.13	TSL:1	c.-410A>G	5_prime_UTR	Exon 1 of 7	ENSP00000253144.9

Frequencies

GnomAD3 genomes

AF:

0.632

AC:

95949

AN:

151754

Hom.:

30897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.764

Gnomad AMI

AF:

0.571

Gnomad AMR

AF:

0.562

Gnomad ASJ

AF:

0.677

Gnomad EAS

AF:

0.507

Gnomad SAS

AF:

0.613

Gnomad FIN

AF:

0.535

Gnomad MID

AF:

0.656

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.629

GnomAD4 exome

AF:

0.696

AC:

AN:

Hom.:

Cov.:

AF XY:

0.700

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.781

AC:

AN:

Other (OTH)

AF:

0.833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.632

AC:

96011

AN:

151874

Hom.:

30918

Cov.:

AF XY:

0.629

AC XY:

46696

AN XY:

74192

show subpopulations

African (AFR)

AF:

0.764

AC:

31646

AN:

41434

American (AMR)

AF:

0.561

AC:

8579

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.677

AC:

2345

AN:

3464

East Asian (EAS)

AF:

0.507

AC:

2592

AN:

5114

South Asian (SAS)

AF:

0.613

AC:

2952

AN:

4816

European-Finnish (FIN)

AF:

0.535

AC:

5636

AN:

10540

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.592

AC:

40235

AN:

67916

Other (OTH)

AF:

0.627

AC:

1324

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1774

3548

5321

7095

8869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.610

Hom.:

18463

Bravo

AF:

0.641

Asia WGS

AF:

0.546

AC:

1895

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

3.1

(source)

DANN

Benign

0.41

PhyloP100

-0.93

PromoterAI

0.015

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

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