rs61730637

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001190417.2(ZNF674):c.1013C>T(p.Thr338Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,209,660 control chromosomes in the GnomAD database, including 212 homozygotes. There are 2,032 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 Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T338T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.030 ( 112 hom., 955 hem., cov: 23)

Exomes 𝑓: 0.0035 ( 100 hom. 1077 hem. )

Consequence

ZNF674
NM_001190417.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.596

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: XL Classification: NO_KNOWN Submitted by: Ambry Genetics
X-linked intellectual disability
Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ZNF674 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025901496).

BP6

Variant X-46500561-G-A is Benign according to our data. Variant chrX-46500561-G-A is described in ClinVar as Benign. ClinVar VariationId is 130843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0978 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190417.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF674	NM_001190417.2	MANE Select	c.1013C>T	p.Thr338Met	missense	Exon 6 of 6	NP_001177346.1	A0A804HHU7
ZNF674	NM_001039891.3		c.1028C>T	p.Thr343Met	missense	Exon 6 of 6	NP_001034980.1	Q2M3X9-1
ZNF674	NM_001146291.2		c.1010C>T	p.Thr337Met	missense	Exon 6 of 6	NP_001139763.1	Q2M3X9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF674	ENST00000683375.1	MANE Select	c.1013C>T	p.Thr338Met	missense	Exon 6 of 6	ENSP00000506769.1	A0A804HHU7
ZNF674	ENST00000523374.5	TSL:1	c.1028C>T	p.Thr343Met	missense	Exon 6 of 6	ENSP00000429148.1	Q2M3X9-1
ZNF674	ENST00000878263.1		c.1013C>T	p.Thr338Met	missense	Exon 6 of 6	ENSP00000548322.1

Frequencies

GnomAD3 genomes

AF:

0.0295

AC:

3319

AN:

112492

Hom.:

110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00844

Gnomad NFE

AF:

0.000937

Gnomad OTH

AF:

0.0190

GnomAD2 exomes

AF:

0.00838

AC:

1518

AN:

181144

AF XY:

0.00569

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.00500

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000669

Gnomad OTH exome

AF:

0.00539

GnomAD4 exome

AF:

0.00351

AC:

3846

AN:

1097117

Hom.:

100

Cov.:

AF XY:

0.00297

AC XY:

1077

AN XY:

362593

show subpopulations

African (AFR)

AF:

0.101

AC:

2659

AN:

26384

American (AMR)

AF:

0.00648

AC:

228

AN:

35202

Ashkenazi Jewish (ASJ)

AF:

0.000103

AC:

AN:

19380

East Asian (EAS)

AF:

0.00

AC:

AN:

30201

South Asian (SAS)

AF:

0.000591

AC:

AN:

54119

European-Finnish (FIN)

AF:

0.0000494

AC:

AN:

40473

Middle Eastern (MID)

AF:

0.00750

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.000617

AC:

519

AN:

841174

Other (OTH)

AF:

0.00810

AC:

373

AN:

46049

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

175

350

524

699

874

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0298

AC:

3350

AN:

112543

Hom.:

112

Cov.:

AF XY:

0.0275

AC XY:

955

AN XY:

34723

show subpopulations

African (AFR)

AF:

0.101

AC:

3121

AN:

30963

American (AMR)

AF:

0.0135

AC:

144

AN:

10629

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3586

South Asian (SAS)

AF:

0.00146

AC:

AN:

2731

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6176

Middle Eastern (MID)

AF:

0.00926

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.000937

AC:

AN:

53362

Other (OTH)

AF:

0.0188

AC:

AN:

1543

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

111

222

332

443

554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0133

Hom.:

409

Bravo

AF:

0.0332

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0919

AC:

300

ESP6500EA

AF:

0.000618

AC:

ExAC

AF:

0.00913

AC:

1104

EpiCase

AF:

0.000927

EpiControl

AF:

0.00101

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

not provided (1)

ZNF674-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.94

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.55

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.0061

FATHMM_MKL

Benign

0.000050

LIST_S2

Benign

0.095

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

-0.60

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.45

REVEL

Benign

0.27

Sift

Benign

0.037

Sift4G

Uncertain

0.015

Polyphen

0.99

Vest4

0.058

MVP

0.38

MPC

0.35

ClinPred

0.015

GERP RS

-4.9

Varity_R

0.016

gMVP

0.050

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over