X-46500505-G-T

Position:

chrX-46500505-G-T

Variant summary

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

The NM_001190417.2(ZNF674):c.1069C>A(p.His357Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,210,446 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 37 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00012 ( 0 hom. 31 hem. )

Consequence

ZNF674
NM_001190417.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 1.34

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=0.007669717).

BP6

Variant X-46500505-G-T is Benign according to our data. Variant chrX-46500505-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1206390.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-46500505-G-T is described in Lovd as [Likely_benign]. Variant chrX-46500505-G-T is described in Lovd as [Benign].

BS2

High Hemizygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF674	NM_001190417.2 linkuse as main transcript	c.1069C>A	p.His357Asn	missense_variant	6/6	ENST00000683375.1	NP_001177346.1
ZNF674	NM_001039891.3 linkuse as main transcript	c.1084C>A	p.His362Asn	missense_variant	6/6		NP_001034980.1
ZNF674	NM_001146291.2 linkuse as main transcript	c.1066C>A	p.His356Asn	missense_variant	6/6		NP_001139763.1
ZNF674	XM_011543943.4 linkuse as main transcript	c.1081C>A	p.His361Asn	missense_variant	6/6		XP_011542245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF674	ENST00000683375.1 linkuse as main transcript	c.1069C>A	p.His357Asn	missense_variant	6/6		NM_001190417.2	ENSP00000506769	A1
ZNF674	ENST00000523374.5 linkuse as main transcript	c.1084C>A	p.His362Asn	missense_variant	6/6	1		ENSP00000429148	P4	Q2M3X9-1
ZNF674	ENST00000414387.6 linkuse as main transcript	c.1066C>A	p.His356Asn	missense_variant	5/5	3		ENSP00000428248	A1	Q2M3X9-2

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

112644

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

AN XY:

34804

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000942

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00501

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000248

AC:

AN:

181159

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

67119

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00322

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000118

AC:

129

AN:

1097748

Hom.:

Cov.:

AF XY:

0.0000854

AC XY:

AN XY:

363182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00381

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000107

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.000177

AC:

AN:

112698

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

AN XY:

34868

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000941

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00502

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000187

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000378

Hom.:

Bravo

AF:

0.000283

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000154

AC:

ExAC

AF:

0.000273

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.6

DANN

Benign

0.64

DEOGEN2

Benign

0.015

T;.

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.18

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.0077

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.34

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.92

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.96

D;.

Vest4

0.20

MVP

0.34

MPC

0.51

ClinPred

0.050

GERP RS

-0.62

Varity_R

0.094

gMVP

0.025

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