Genetic Variant ZNF331:c.-204-1938G>C (chr19-53537278-G-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.-204-1938G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,132 control chromosomes in the GnomAD database, including 5,992 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 0.26 ( 5987 hom., cov: 32)

Exomes 𝑓: 0.31 ( 5 hom. )

Consequence

ZNF331
ENST00000253144.13 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.182

Publications

3 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 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.-234-1938G>C	intron	N/A	NP_001304049.1
ZNF331	NM_018555.6	c.-204-1938G>C	intron	N/A	NP_061025.5
ZNF331	NM_001317114.2	c.-682G>C	upstream_gene	N/A	NP_001304043.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZNF331	ENST00000253144.13	TSL:1	c.-204-1938G>C	intron	N/A	ENSP00000253144.9
ZNF331	ENST00000502248.5	TSL:1	c.-234-1938G>C	intron	N/A	ENSP00000423675.1
ZNF331	ENST00000504033.5	TSL:5	n.26G>C	non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39362

AN:

151950

Hom.:

5966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.314

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.228

GnomAD4 exome

AF:

0.313

AC:

AN:

Hom.:

Cov.:

AF XY:

0.328

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.283

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.560

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.259

AC:

39418

AN:

152068

Hom.:

5987

Cov.:

AF XY:

0.255

AC XY:

18974

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.420

AC:

17407

AN:

41454

American (AMR)

AF:

0.190

AC:

2907

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

698

AN:

3464

East Asian (EAS)

AF:

0.314

AC:

1623

AN:

5166

South Asian (SAS)

AF:

0.212

AC:

1022

AN:

4824

European-Finnish (FIN)

AF:

0.151

AC:

1596

AN:

10590

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.195

AC:

13285

AN:

67986

Other (OTH)

AF:

0.228

AC:

482

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1428

2856

4284

5712

7140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.118

Hom.:

219

Bravo

AF:

0.266

Asia WGS

AF:

0.259

AC:

897

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.4

(source)

DANN

Benign

0.40

PhyloP100

-0.18

PromoterAI

0.040

Neutral

(source)

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