Variant 16-3404613-T-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.590T>C(p.Leu197Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000954 in 1,614,178 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000099 ( 1 hom. )

Consequence

ZNF174
NM_003450.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.602

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=0.026744425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF174	NM_003450.3 linkuse as main transcript	c.590T>C	p.Leu197Pro	missense_variant	2/3	ENST00000268655.5	NP_003441.1	Q15697-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF174	ENST00000268655.5 linkuse as main transcript	c.590T>C	p.Leu197Pro	missense_variant	2/3	1	NM_003450.3	ENSP00000268655.4		Q15697-1
ENSG00000285329	ENST00000575785.2 linkuse as main transcript	n.176T>C		non_coding_transcript_exon_variant	2/5	4		ENSP00000477472.1		V9GZ69

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251330

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000707

Gnomad SAS 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:

0.0000992

AC:

145

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000949

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000926

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000576

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

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

Jul 19, 2023

The c.590T>C (p.L197P) alteration is located in exon 2 (coding exon 2) of the ZNF174 gene. This alteration results from a T to C substitution at nucleotide position 590, causing the leucine (L) at amino acid position 197 to be replaced by a proline (P). 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

0.14

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.044

.;T;.;T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.55

.;.;T;T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.027

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.81

L;L;L;L;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.70

.;.;N;N;.

REVEL

Benign

0.069

Sift

Benign

0.10

.;.;T;D;.

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.041

B;B;B;B;.

Vest4

0.24

MVP

0.27

MPC

0.41

ClinPred

0.041

GERP RS

4.2

Varity_R

0.051

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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