Variant chr16-3408376-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003450.3(ZNF174):c.681A>C(p.Lys227Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Consequence

ZNF174
NM_003450.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.222

Variant links:

Genes affected

ZNF174 (HGNC:12963): (zinc finger protein 174) This gene encodes a protein with three Cys2-His2-type zinc fingers in the carboxy-terminus, a putative nuclear localization signal, and an amino-terminus SCAN box which forms homodimers. This protein is believed to function as a transcriptional repressor. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2016]

ZNF174 links:

ENSG00000285329 (HGNC:):

ENSG00000285329 links:

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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=0.06697571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF174	NM_003450.3 linkuse as main transcript	c.681A>C	p.Lys227Asn	missense_variant	3/3	ENST00000268655.5	NP_003441.1	Q15697-1
ZNF174	NM_001347868.2 linkuse as main transcript	c.681A>C	p.Lys227Asn	missense_variant	4/4		NP_001334797.1	Q15697-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF174	ENST00000268655.5 linkuse as main transcript	c.681A>C	p.Lys227Asn	missense_variant	3/3	1	NM_003450.3	ENSP00000268655.4	Q15697-1
ENSG00000285329	ENST00000575785.2 linkuse as main transcript	n.211+3728A>C		intron_variant		4		ENSP00000477472.1	V9GZ69
ZNF174	ENST00000571936.5 linkuse as main transcript	c.681A>C	p.Lys227Asn	missense_variant	4/4	5		ENSP00000460397.1	Q15697-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250788

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135556

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:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

The c.681A>C (p.K227N) alteration is located in exon 3 (coding exon 3) of the ZNF174 gene. This alteration results from a A to C substitution at nucleotide position 681, causing the lysine (K) at amino acid position 227 to be replaced by an asparagine (N). 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

0.40

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.051

T;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.54

.;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

L;L

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.5

.;N

REVEL

Benign

0.031

Sift

Benign

0.33

.;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0010

B;B

Vest4

0.054

MutPred

0.42

Loss of ubiquitination at K227 (P = 0.0011);Loss of ubiquitination at K227 (P = 0.0011);

MVP

0.24

MPC

0.49

ClinPred

0.032

GERP RS

2.3

Varity_R

0.12

gMVP

0.28

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