Genetic Variant ZNF396:p.Arg298Gln (chr18-35369330-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001322286.2(ZNF396):c.893G>A(p.Arg298Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ZNF396
NM_001322286.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0200

Publications

0 publications found

Variant links:

Genes affected

ZNF396 (HGNC:18824): (zinc finger protein 396) Enables protein heterodimerization activity; protein homodimerization activity; and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription, DNA-templated. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF396 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05948335).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322286.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF396	NM_001322286.2	MANE Select	c.893G>A	p.Arg298Gln	missense	Exon 4 of 4	NP_001309215.1	Q96N95-1
ZNF396	NM_001322290.2		c.893G>A	p.Arg298Gln	missense	Exon 5 of 5	NP_001309219.1	Q96N95-1
ZNF396	NM_145756.3		c.893G>A	p.Arg298Gln	missense	Exon 4 of 5	NP_665699.1	Q96N95-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF396	ENST00000589332.7	TSL:1 MANE Select	c.893G>A	p.Arg298Gln	missense	Exon 4 of 4	ENSP00000466500.1	Q96N95-1
ZNF396	ENST00000306346.5	TSL:1	c.893G>A	p.Arg298Gln	missense	Exon 4 of 5	ENSP00000302310.1	Q96N95-3
ZNF396	ENST00000862521.1		c.893G>A	p.Arg298Gln	missense	Exon 5 of 5	ENSP00000532580.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251486

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.000104

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.78

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.0047

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.74

M_CAP

Benign

0.0055

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.17

PhyloP100

0.020

PrimateAI

Benign

0.24

PROVEAN

Benign

0.92

REVEL

Benign

0.078

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.086

Vest4

0.046

MutPred

0.60

Loss of MoRF binding (P = 0.0296)

MVP

0.14

MPC

0.13

ClinPred

0.024

GERP RS

1.1

Varity_R

0.015

gMVP

0.025

Mutation Taster

=99/1

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over