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 ENST00000253144.13(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
ENST00000253144.13 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
ZNF331	NM_018555.6 link	c.-225T>C	5_prime_UTR_variant	Exon 2 of 7	NP_061025.5	Q9NQX6A0A024R4J5Q68D63
ZNF331	XM_011527076.4 link	c.-656T>C	5_prime_UTR_variant	Exon 2 of 8	XP_011525378.1	Q9NQX6A0A024R4J5
ZNF331	XM_011527078.4 link	c.-255T>C	5_prime_UTR_variant	Exon 2 of 8	XP_011525380.1	Q9NQX6A0A024R4J5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ZNF331	ENST00000253144.13 link	c.-225T>C	5_prime_UTR_variant	Exon 2 of 7	1	ENSP00000253144.9	Q9NQX6
ZNF331	ENST00000502248.5 link	c.-235+580T>C	intron_variant	Intron 1 of 6	1	ENSP00000423675.1	E7EV14
ZNF331	ENST00000513929.6 link	n.1150T>C	non_coding_transcript_exon_variant	Exon 2 of 3	2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over