Genetic Variant ZNF391:p.Asp72Glu (chr6-27400586-C-A) – 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_001076781.3(ZNF391):c.216C>A(p.Asp72Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,858 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF391
NM_001076781.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.17

Publications

0 publications found

Variant links:

Genes affected

ZNF391 (HGNC:18779): (zinc finger protein 391) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF391 links:

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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=0.04931146).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001076781.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF391	NM_001076781.3	MANE Select	c.216C>A	p.Asp72Glu	missense	Exon 3 of 3	NP_001070249.1	Q9UJN7
ZNF391	NM_001322288.2		c.216C>A	p.Asp72Glu	missense	Exon 4 of 4	NP_001309217.1	Q9UJN7
ZNF391	NM_001322289.2		c.216C>A	p.Asp72Glu	missense	Exon 4 of 4	NP_001309218.1	Q9UJN7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF391	ENST00000244576.9	TSL:2 MANE Select	c.216C>A	p.Asp72Glu	missense	Exon 3 of 3	ENSP00000244576.4	Q9UJN7
ZNF391	ENST00000901127.1		c.216C>A	p.Asp72Glu	missense	Exon 3 of 3	ENSP00000571186.1
ZNF391	ENST00000901128.1		c.216C>A	p.Asp72Glu	missense	Exon 2 of 2	ENSP00000571187.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1112002

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0030

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.0057

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.14

M_CAP

Benign

0.00072

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

PhyloP100

-4.2

PrimateAI

Benign

0.21

PROVEAN

Benign

0.060

REVEL

Benign

0.014

Sift

Benign

0.45

Sift4G

Benign

0.69

Polyphen

0.0020

Vest4

0.017

MutPred

0.20

Gain of helix (P = 0.132)

MVP

0.099

MPC

0.12

ClinPred

0.047

GERP RS

-8.1

Varity_R

0.038

gMVP

0.016

Mutation Taster

=98/2

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over