Genetic Variant ZNF107:p.Asn159Asp (chr7-64706572-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001282359.2(ZNF107):c.475A>G(p.Asn159Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000436 in 1,607,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZNF107
NM_001282359.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.426

Publications

0 publications found

Variant links:

Genes affected

ZNF107 (HGNC:12887): (zinc finger protein 107) This gene encodes a protein containing multiple C2H2-type zinc finger regions. Proteins containing zinc fingers may act as transcriptional regulators, but may also have other cellular functions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ZNF107 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13725764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF107	NM_001282359.2 link	c.475A>G	p.Asn159Asp	missense_variant	Exon 4 of 4	ENST00000620827.6	NP_001269288.1	A0A0B4J2G0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF107	ENST00000620827.6 link	c.475A>G	p.Asn159Asp	missense_variant	Exon 4 of 4	4	NM_001282359.2	ENSP00000483720.1		A0A0B4J2G0

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000411

AC:

AN:

243544

AF XY:

0.00000759

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1454922

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33006

American (AMR)

AF:

0.00

AC:

AN:

42974

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25722

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00000451

AC:

AN:

1109856

Other (OTH)

AF:

0.00

AC:

AN:

60020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 17, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.268A>G (p.N90D) alteration is located in exon 7 (coding exon 2) of the ZNF107 gene. This alteration results from a A to G substitution at nucleotide position 268, causing the asparagine (N) at amino acid position 90 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

T;.;T;T;T;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.00018

LIST_S2

Benign

0.20

T;T;T;.;T;.

M_CAP

Benign

0.0077

MetaRNN

Benign

0.14

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

.;.;.;M;M;M

PhyloP100

0.43

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-4.5

.;.;D;D;D;D

REVEL

Benign

0.014

Sift

Uncertain

0.0060

.;.;D;T;T;T

Sift4G

Benign

0.34

T;T;D;T;T;T

Polyphen

1.0

.;.;.;D;D;D

Vest4

0.12

MutPred

0.34

.;.;Loss of MoRF binding (P = 0.0746);Loss of MoRF binding (P = 0.0746);Loss of MoRF binding (P = 0.0746);Loss of MoRF binding (P = 0.0746);

MVP

0.040

MPC

0.035

ClinPred

0.70

GERP RS

0.92

Varity_R

0.21

gMVP

0.0043

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over