Variant X-46500560-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001190417.2(ZNF674):c.1014G>A(p.Thr338=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,209,763 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 89 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.00023 ( 0 hom. 85 hem. )

Consequence

ZNF674
NM_001190417.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0430

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 (BayesDel_noAF=-0.8).

BP6

Variant X-46500560-C-T is Benign according to our data. Variant chrX-46500560-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3039339.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.043 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF674	NM_001190417.2 linkuse as main transcript	c.1014G>A	p.Thr338=	synonymous_variant	6/6	ENST00000683375.1	NP_001177346.1
ZNF674	NM_001039891.3 linkuse as main transcript	c.1029G>A	p.Thr343=	synonymous_variant	6/6		NP_001034980.1
ZNF674	NM_001146291.2 linkuse as main transcript	c.1011G>A	p.Thr337=	synonymous_variant	6/6		NP_001139763.1
ZNF674	XM_011543943.4 linkuse as main transcript	c.1026G>A	p.Thr342=	synonymous_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.1014G>A	p.Thr338=	synonymous_variant	6/6		NM_001190417.2	ENSP00000506769	A1
ZNF674	ENST00000523374.5 linkuse as main transcript	c.1029G>A	p.Thr343=	synonymous_variant	6/6	1		ENSP00000429148	P4	Q2M3X9-1
ZNF674	ENST00000414387.6 linkuse as main transcript	c.1011G>A	p.Thr337=	synonymous_variant	5/5	3		ENSP00000428248	A1	Q2M3X9-2

Frequencies

GnomAD3 genomes

AF:

0.000196

AC:

AN:

112528

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34692

show subpopulations

Gnomad AFR

AF:

0.000129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000658

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000127

AC:

AN:

181122

Hom.:

AF XY:

0.000209

AC XY:

AN XY:

67098

show subpopulations

Gnomad AFR exome

AF:

0.0000806

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000525

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000223

Gnomad OTH exome

AF:

0.000450

GnomAD4 exome

AF:

0.000229

AC:

251

AN:

1097235

Hom.:

Cov.:

AF XY:

0.000234

AC XY:

AN XY:

362683

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000852

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000264

Gnomad4 OTH exome

AF:

0.000478

GnomAD4 genome

AF:

0.000196

AC:

AN:

112528

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34692

show subpopulations

Gnomad4 AFR

AF:

0.000129

Gnomad4 AMR

AF:

0.000658

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.000336

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZNF674-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 23, 2019

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_noAF

Benign

-0.80

CADD

Benign

0.94

DANN

Benign

0.48

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