Variant X-46500524-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001190417.2(ZNF674):c.1050G>C(p.Glu350Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,097,663 control chromosomes in the GnomAD database, including 1 homozygotes. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000015 ( 1 hom. 6 hem. )

Consequence

ZNF674
NM_001190417.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.244

Variant links:

Genes affected

ZNF674 (HGNC:17625): (zinc finger protein 674) This gene encodes a zinc finger protein with an N-terminal Kruppel-associated box-containing (KRAB) domain and 11 Kruppel-type C2H2 zinc finger domains. Like other zinc finger proteins, this gene may function as a transcription factor. This gene resides on an area of chromosome X that has been implicated in nonsyndromic X-linked cognitive disabilities. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]

ZNF674 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12817839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF674	NM_001190417.2 linkuse as main transcript	c.1050G>C	p.Glu350Asp	missense_variant	6/6	ENST00000683375.1
ZNF674	NM_001039891.3 linkuse as main transcript	c.1065G>C	p.Glu355Asp	missense_variant	6/6
ZNF674	NM_001146291.2 linkuse as main transcript	c.1047G>C	p.Glu349Asp	missense_variant	6/6
ZNF674	XM_011543943.4 linkuse as main transcript	c.1062G>C	p.Glu354Asp	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF674	ENST00000683375.1 linkuse as main transcript	c.1050G>C	p.Glu350Asp	missense_variant	6/6		NM_001190417.2	A1
ZNF674	ENST00000523374.5 linkuse as main transcript	c.1065G>C	p.Glu355Asp	missense_variant	6/6	1		P4	Q2M3X9-1
ZNF674	ENST00000414387.6 linkuse as main transcript	c.1047G>C	p.Glu349Asp	missense_variant	5/5	3		A1	Q2M3X9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

181103

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67101

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:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1097663

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

363097

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000296

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000248

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

Aug 12, 2021

The c.1065G>C (p.E355D) alteration is located in exon 6 (coding exon 4) of the ZNF674 gene. This alteration results from a G to C substitution at nucleotide position 1065, causing the glutamic acid (E) at amino acid position 355 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

0.12

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.89

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.057

T;.

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.36

T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.063

Sift

Benign

0.046

D;T

Sift4G

Uncertain

0.046

D;T

Polyphen

1.0

D;.

Vest4

0.070

MutPred

0.41

Gain of ubiquitination at K356 (P = 0.143);.;

MVP

0.27

MPC

0.19

ClinPred

0.082

GERP RS

1.8

Varity_R

0.12

gMVP

0.029

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