Variant X-46500265-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_001190417.2(ZNF674):c.1309G>T(p.Glu437Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000628 in 1,209,720 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.000035 ( 0 hom. 7 hem. )

Consequence

ZNF674
NM_001190417.2 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.40

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 -4 ACMG points.

PM4

Stoplost variant in NM_001190417.2 Downstream stopcodon found after 8 codons.

BP6

Variant X-46500265-C-A is Benign according to our data. Variant chrX-46500265-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3036471.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF674	NM_001190417.2 linkuse as main transcript	c.1309G>T	p.Glu437Ter	stop_gained	6/6	ENST00000683375.1
ZNF674	NM_001039891.3 linkuse as main transcript	c.1324G>T	p.Glu442Ter	stop_gained	6/6
ZNF674	NM_001146291.2 linkuse as main transcript	c.1306G>T	p.Glu436Ter	stop_gained	6/6
ZNF674	XM_011543943.4 linkuse as main transcript	c.1321G>T	p.Glu441Ter	stop_gained	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF674	ENST00000683375.1 linkuse as main transcript	c.1309G>T	p.Glu437Ter	stop_gained	6/6		NM_001190417.2	A1
ZNF674	ENST00000523374.5 linkuse as main transcript	c.1324G>T	p.Glu442Ter	stop_gained	6/6	1		P4	Q2M3X9-1
ZNF674	ENST00000414387.6 linkuse as main transcript	c.1306G>T	p.Glu436Ter	stop_gained	5/5	3		A1	Q2M3X9-2

Frequencies

GnomAD3 genomes

AF:

0.000340

AC:

AN:

111825

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

AN XY:

34023

show subpopulations

Gnomad AFR

AF:

0.00124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000826

AC:

AN:

181584

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

67236

show subpopulations

Gnomad AFR exome

AF:

0.00120

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000346

AC:

AN:

1097841

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363229

show subpopulations

Gnomad4 AFR exome

AF:

0.00129

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.000340

AC:

AN:

111879

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

AN XY:

34087

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000576

Hom.:

Bravo

AF:

0.000363

ESP6500AA

AF:

0.00132

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

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

Feb 21, 2022

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

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Pathogenic

0.23

Cadd

Pathogenic

Dann

Uncertain

1.0

FATHMM_MKL

Benign

0.000070

MutationTaster

Benign

1.0

D;D

Vest4

0.065

GERP RS

2.2

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