dbSNP rs8100338: ZNF331:c.-417C>G (chr19-53521940-C-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.-417C>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 0.319 in 151,996 control chromosomes in the GnomAD database, including 7,895 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 ( 7887 hom., cov: 32)

Exomes 𝑓: 0.47 ( 8 hom. )

Consequence

ZNF331
ENST00000253144.13 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

5 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:

Genome browser will be placed here

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=-0.9).

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_001317120.2 link	c.-379C>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	NP_001304049.1	Q9NQX6A0A024R4J5Q71QC4Q68D63
ZNF331	NM_018555.6 link	c.-417C>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	NP_061025.5	Q9NQX6A0A024R4J5Q68D63
ZNF331	XM_011527076.4 link	c.-848C>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	XP_011525378.1	Q9NQX6A0A024R4J5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ZNF331	ENST00000253144.13 link	c.-417C>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	1	ENSP00000253144.9	Q9NQX6
ZNF331	ENST00000502248.5 link	c.-379C>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	1	ENSP00000423675.1	E7EV14
ZNF331	ENST00000253144.13 link	c.-417C>G	5_prime_UTR_variant	Exon 1 of 7	1	ENSP00000253144.9	Q9NQX6

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48483

AN:

151810

Hom.:

7884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.347

GnomAD4 exome

AF:

0.471

AC:

AN:

Hom.:

Cov.:

AF XY:

0.405

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

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:

0.458

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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:

0.319

AC:

48497

AN:

151928

Hom.:

7887

Cov.:

AF XY:

0.320

AC XY:

23751

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.343

AC:

14219

AN:

41420

American (AMR)

AF:

0.315

AC:

4816

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

1437

AN:

3472

East Asian (EAS)

AF:

0.193

AC:

991

AN:

5140

South Asian (SAS)

AF:

0.388

AC:

1872

AN:

4820

European-Finnish (FIN)

AF:

0.287

AC:

3037

AN:

10580

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.310

AC:

21056

AN:

67922

Other (OTH)

AF:

0.346

AC:

729

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1683

3365

5048

6730

8413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.300

Hom.:

909

Bravo

AF:

0.326

Asia WGS

AF:

0.283

AC:

983

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.59

(source)

DANN

Benign

0.40

PhyloP100

-1.1

PromoterAI

0.0027

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over