X-46499955-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001190417.2(ZNF674):c.1619G>T(p.Arg540Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,200,287 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 61 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., 33 hem., cov: 23)

Exomes 𝑓: 0.00010 ( 0 hom. 28 hem. )

Consequence

ZNF674
NM_001190417.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.09

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013307571).

BP6

Variant X-46499955-C-A is Benign according to our data. Variant chrX-46499955-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3034837.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd at 33 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF674	NM_001190417.2 linkuse as main transcript	c.1619G>T	p.Arg540Ile	missense_variant	6/6	ENST00000683375.1
ZNF674	NM_001039891.3 linkuse as main transcript	c.1634G>T	p.Arg545Ile	missense_variant	6/6
ZNF674	NM_001146291.2 linkuse as main transcript	c.1616G>T	p.Arg539Ile	missense_variant	6/6
ZNF674	XM_011543943.4 linkuse as main transcript	c.1631G>T	p.Arg544Ile	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF674	ENST00000683375.1 linkuse as main transcript	c.1619G>T	p.Arg540Ile	missense_variant	6/6		NM_001190417.2	A1
ZNF674	ENST00000523374.5 linkuse as main transcript	c.1634G>T	p.Arg545Ile	missense_variant	6/6	1		P4	Q2M3X9-1
ZNF674	ENST00000414387.6 linkuse as main transcript	c.1616G>T	p.Arg539Ile	missense_variant	5/5	3		A1	Q2M3X9-2

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

123

AN:

111872

Hom.:

Cov.:

AF XY:

0.000969

AC XY:

AN XY:

34042

show subpopulations

Gnomad AFR

AF:

0.00393

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000951

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000265

AC:

AN:

169563

Hom.:

AF XY:

0.000231

AC XY:

AN XY:

56187

show subpopulations

Gnomad AFR exome

AF:

0.00357

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:

0.0000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

110

AN:

1088363

Hom.:

Cov.:

AF XY:

0.0000787

AC XY:

AN XY:

355607

show subpopulations

Gnomad4 AFR exome

AF:

0.00374

Gnomad4 AMR exome

AF:

0.0000579

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000239

Gnomad4 OTH exome

AF:

0.000153

GnomAD4 genome

AF:

0.00110

AC:

123

AN:

111924

Hom.:

Cov.:

AF XY:

0.000968

AC XY:

AN XY:

34104

show subpopulations

Gnomad4 AFR

AF:

0.00392

Gnomad4 AMR

AF:

0.0000950

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.00113

ESP6500AA

AF:

0.00422

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000313

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ZNF674-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 14, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.056

T;.

FATHMM_MKL

Benign

0.00062

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

0.64

N;N

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-6.9

D;D

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.32

MVP

0.78

MPC

1.1

ClinPred

0.19

GERP RS

1.6

Varity_R

0.64

gMVP

0.17

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