Genetic Variant ZNF7:p.Ala93Val (chr8-144841385-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_003416.4(ZNF7):c.278C>T(p.Ala93Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,458,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ZNF7
NM_003416.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.223

Publications

0 publications found

Variant links:

Genes affected

ZNF7 (HGNC:13139): (zinc finger protein 7) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be integral component of membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF7 links:

COMMD5 (HGNC:17902): (COMM domain containing 5) Predicted to be involved in proximal tubule morphogenesis. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

COMMD5 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=0.038175434).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003416.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF7	NM_003416.4	MANE Select	c.278C>T	p.Ala93Val	missense	Exon 5 of 5	NP_003407.1	P17097-1
ZNF7	NM_001349809.2		c.341C>T	p.Ala114Val	missense	Exon 4 of 4	NP_001336738.1
ZNF7	NM_001349806.2		c.329C>T	p.Ala110Val	missense	Exon 5 of 5	NP_001336735.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF7	ENST00000532777.6	TSL:1 MANE Select	c.278C>T	p.Ala93Val	missense	Exon 5 of 5	ENSP00000432641.2	P17097-1
ZNF7	ENST00000446747.7	TSL:1	c.311C>T	p.Ala104Val	missense	Exon 5 of 5	ENSP00000393260.2	P17097-2
ZNF7	ENST00000528372.5	TSL:1	c.278C>T	p.Ala93Val	missense	Exon 5 of 5	ENSP00000432724.1	P17097-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251100

AF XY:

0.00000737

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:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1458964

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33438

American (AMR)

AF:

0.00

AC:

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39588

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86206

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1109614

Other (OTH)

AF:

0.00

AC:

AN:

60254

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.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

0.077

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.8

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.51

M_CAP

Benign

0.0029

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.4

PhyloP100

0.22

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.1

REVEL

Benign

0.054

Sift

Benign

0.049

Sift4G

Benign

0.26

Polyphen

0.0010

Vest4

0.055

MutPred

0.22

Gain of catalytic residue at A93 (P = 0.0191)

MVP

0.26

MPC

0.085

ClinPred

0.031

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.10

Mutation Taster

=97/3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over