Genetic Variant NM_001079906.2:c.1185A>G (chr19-53577745-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001079906.2(ZNF331):c.1185A>G(p.Gly395Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 1,614,054 control chromosomes in the GnomAD database, including 5,042 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 0.10 ( 1216 hom., cov: 33)

Exomes 𝑓: 0.066 ( 3826 hom. )

Consequence

ZNF331
NM_001079906.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.23

Publications

9 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:

ENSG00000290755 (HGNC:):

ENSG00000290755 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP7

Synonymous conserved (PhyloP=-4.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF331	NM_001079906.2 link	c.1185A>G	p.Gly395Gly	synonymous_variant	Exon 6 of 6	ENST00000449416.6	NP_001073375.1	Q9NQX6A0A024R4J5Q71QC5Q68D63

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF331	ENST00000449416.6 link	c.1185A>G	p.Gly395Gly	synonymous_variant	Exon 6 of 6	5	NM_001079906.2	ENSP00000393817.1		Q9NQX6

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15760

AN:

152066

Hom.:

1217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.0264

Gnomad AMR

AF:

0.0661

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.0531

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0664

Gnomad OTH

AF:

0.104

GnomAD2 exomes

AF:

0.0606

AC:

15235

AN:

251376

AF XY:

0.0568

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.0383

Gnomad ASJ exome

AF:

0.0675

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0555

Gnomad NFE exome

AF:

0.0660

Gnomad OTH exome

AF:

0.0589

GnomAD4 exome

AF:

0.0657

AC:

96009

AN:

1461870

Hom.:

3826

Cov.:

AF XY:

0.0634

AC XY:

46097

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.229

AC:

7669

AN:

33478

American (AMR)

AF:

0.0423

AC:

1893

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0653

AC:

1707

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39698

South Asian (SAS)

AF:

0.0170

AC:

1466

AN:

86258

European-Finnish (FIN)

AF:

0.0523

AC:

2796

AN:

53418

Middle Eastern (MID)

AF:

0.0695

AC:

401

AN:

5768

European-Non Finnish (NFE)

AF:

0.0682

AC:

75843

AN:

1111998

Other (OTH)

AF:

0.0700

AC:

4230

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

6075

12150

18226

24301

30376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2888

5776

8664

11552

14440

<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:

0.104

AC:

15778

AN:

152184

Hom.:

1216

Cov.:

AF XY:

0.102

AC XY:

7565

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.220

AC:

9133

AN:

41502

American (AMR)

AF:

0.0660

AC:

1009

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0608

AC:

211

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.0180

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0531

AC:

564

AN:

10614

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0664

AC:

4514

AN:

67990

Other (OTH)

AF:

0.103

AC:

217

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

684

1367

2051

2734

3418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<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:

0.0777

Hom.:

1221

Bravo

AF:

0.110

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0687

EpiControl

AF:

0.0717

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.68

(source)

DANN

Benign

0.60

PhyloP100

-4.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over