Genetic Variant NM_030895.3:c.650C>T (chr8-143296325-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030895.3(ZNF696):c.650C>T(p.Ala217Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,596,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 35)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ZNF696
NM_030895.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.694

Variant links:

Genes affected

ZNF696 (HGNC:25872): (zinc finger protein 696) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF696 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038103938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF696	NM_030895.3 link	c.650C>T	p.Ala217Val	missense_variant	Exon 3 of 3	ENST00000330143.8	NP_112157.2	Q9H7X3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF696	ENST00000330143.8 link	c.650C>T	p.Ala217Val	missense_variant	Exon 3 of 3	1	NM_030895.3	ENSP00000328515.3		Q9H7X3
ZNF696	ENST00000518575.5 link	c.*38C>T		downstream_gene_variant		3		ENSP00000427857.1		E5RG39

Frequencies

GnomAD3 genomes

AF:

0.000198

AC:

AN:

151804

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000309

AC:

AN:

220318

Hom.:

AF XY:

0.000295

AC XY:

AN XY:

122020

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000824

Gnomad NFE exome

AF:

0.000562

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.000173

AC:

250

AN:

1444512

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

129

AN XY:

718390

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000388

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.000179

Gnomad4 OTH exome

AF:

0.0000836

GnomAD4 genome

AF:

0.000198

AC:

AN:

151804

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74156

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000946

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000259

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.000439

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.650C>T (p.A217V) alteration is located in exon 3 (coding exon 2) of the ZNF696 gene. This alteration results from a C to T substitution at nucleotide position 650, causing the alanine (A) at amino acid position 217 to be replaced by a valine (V). 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.085

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.40

M_CAP

Benign

0.0054

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.0080

Sift

Uncertain

0.010

Sift4G

Uncertain

0.044

Polyphen

0.82

Vest4

0.059

MVP

0.20

MPC

0.94

ClinPred

0.18

GERP RS

0.59

Varity_R

0.20

gMVP

0.024

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over