Variant rs112855712 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_001079906.2(ZNF331):c.326A>G(p.Lys109Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ZNF331
NM_001079906.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.989

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) (size 0) in uniprot entity ZN331_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14595908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF331	NM_001079906.2 link	c.326A>G	p.Lys109Arg	missense_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.326A>G	p.Lys109Arg	missense_variant	Exon 6 of 6	5	NM_001079906.2	ENSP00000393817.1		Q9NQX6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.1

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.21

.;.;.;.;T;.;.;.;.;.;.;T;.;.;.

M_CAP

Benign

0.0014

MetaRNN

Benign

0.15

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L;L;L;L;L;L;L;L;.;.;L;L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

.;N;.;N;N;N;N;.;N;N;N;N;.;.;.

REVEL

Benign

0.028

Sift

Benign

0.11

.;T;.;T;T;T;T;.;T;T;D;D;.;.;.

Sift4G

Benign

0.23

.;T;.;T;T;T;T;.;T;T;T;T;.;.;.

Polyphen

0.34

B;B;B;B;B;B;B;B;B;B;.;.;B;B;B

Vest4

0.061, 0.070, 0.067, 0.076, 0.068

MutPred

0.36

Loss of methylation at K109 (P = 0.0012);Loss of methylation at K109 (P = 0.0012);Loss of methylation at K109 (P = 0.0012);Loss of methylation at K109 (P = 0.0012);Loss of methylation at K109 (P = 0.0012);Loss of methylation at K109 (P = 0.0012);Loss of methylation at K109 (P = 0.0012);Loss of methylation at K109 (P = 0.0012);Loss of methylation at K109 (P = 0.0012);Loss of methylation at K109 (P = 0.0012);Loss of methylation at K109 (P = 0.0012);Loss of methylation at K109 (P = 0.0012);Loss of methylation at K109 (P = 0.0012);Loss of methylation at K109 (P = 0.0012);Loss of methylation at K109 (P = 0.0012);

MVP

0.37

MPC

0.57

ClinPred

0.17

GERP RS

2.6

Varity_R

0.037

gMVP

0.083

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over