Genetic Variant ENST00000253144.13:c.-323C>G (chr19-53522034-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.-323C>G 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 151,902 control chromosomes in the GnomAD database, including 8,000 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 ( 8000 hom., cov: 31)

Exomes 𝑓: 0.33 ( 0 hom. )

Consequence

ZNF331
ENST00000253144.13 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.546

Publications

7 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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new If you want to explore the variant's impact on the transcript ENST00000253144.13, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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 (SAS) allele frequency at 95% confidence interval = 0.374 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF331	NM_001317120.2		c.-285C>G		5_prime_UTR	Exon 1 of 7	NP_001304049.1	Q9NQX6
	ZNF331	NM_018555.6		c.-323C>G		5_prime_UTR	Exon 1 of 7	NP_061025.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF331	ENST00000253144.13	TSL:1	c.-323C>G	5_prime_UTR	Exon 1 of 7	ENSP00000253144.9	Q9NQX6
ZNF331	ENST00000502248.5	TSL:1	c.-285C>G	5_prime_UTR	Exon 1 of 7	ENSP00000423675.1	E7EV14
ZNF331	ENST00000511593.6	TSL:5	c.-286C>G	5_prime_UTR	Exon 1 of 7	ENSP00000427439.1	Q9NQX6

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48792

AN:

151760

Hom.:

7997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.350

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.348

GnomAD4 exome

AF:

0.333

AC:

AN:

Hom.:

Cov.:

AF XY:

0.389

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)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AF:

0.375

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.556

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:

48806

AN:

151878

Hom.:

8000

Cov.:

AF XY:

0.322

AC XY:

23899

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.349

AC:

14450

AN:

41374

American (AMR)

AF:

0.316

AC:

4831

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

1434

AN:

3466

East Asian (EAS)

AF:

0.194

AC:

992

AN:

5126

South Asian (SAS)

AF:

0.389

AC:

1873

AN:

4818

European-Finnish (FIN)

AF:

0.288

AC:

3040

AN:

10548

Middle Eastern (MID)

AF:

0.418

AC:

122

AN:

292

European-Non Finnish (NFE)

AF:

0.311

AC:

21112

AN:

67964

Other (OTH)

AF:

0.348

AC:

732

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1681

3363

5044

6726

8407

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:

0.301

Hom.:

912

Bravo

AF:

0.328

Asia WGS

AF:

0.283

AC:

983

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

0.48

PhyloP100

-0.55

PromoterAI

-0.020

Neutral

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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