Genetic Variant ZNF331:c.-225T>C (chr19-53522664-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_018555.6(ZNF331):c.-225T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,160 control chromosomes in the GnomAD database, including 8,004 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 0.32 ( 8002 hom., cov: 32)

Exomes 𝑓: 0.83 ( 2 hom. )

Consequence

ZNF331
NM_018555.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.332

Publications

20 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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018555.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF331	NM_018555.6		c.-225T>C		5_prime_UTR	Exon 2 of 7	NP_061025.5
	ZNF331	NM_001317120.2		c.-235+580T>C		intron	N/A	NP_001304049.1	Q9NQX6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF331	ENST00000253144.13	TSL:1	c.-225T>C	5_prime_UTR	Exon 2 of 7	ENSP00000253144.9	Q9NQX6
ZNF331	ENST00000502248.5	TSL:1	c.-235+580T>C	intron	N/A	ENSP00000423675.1	E7EV14
ZNF331	ENST00000511593.6	TSL:5	c.-188T>C	5_prime_UTR	Exon 2 of 7	ENSP00000427439.1	Q9NQX6

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48819

AN:

152036

Hom.:

7999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.244

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.348

GnomAD4 exome

AF:

0.833

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

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:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.321

AC:

48833

AN:

152154

Hom.:

8002

Cov.:

AF XY:

0.321

AC XY:

23924

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.349

AC:

14474

AN:

41490

American (AMR)

AF:

0.316

AC:

4828

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

1436

AN:

3470

East Asian (EAS)

AF:

0.194

AC:

1006

AN:

5186

South Asian (SAS)

AF:

0.389

AC:

1877

AN:

4824

European-Finnish (FIN)

AF:

0.286

AC:

3031

AN:

10588

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.310

AC:

21101

AN:

67990

Other (OTH)

AF:

0.347

AC:

735

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1714

3428

5143

6857

8571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.311

Hom.:

3367

Bravo

AF:

0.328

Asia WGS

AF:

0.283

AC:

985

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.5

(source)

DANN

Benign

0.38

PhyloP100

-0.33

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)

0.060

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