Variant rs200824131 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001190417.2(ZNF674):c.16-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000992 in 1,209,892 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 55 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000098 ( 0 hom. 53 hem. )

Consequence

ZNF674
NM_001190417.2 splice_region, intron

Scores

Splicing: ADA: 0.0001517

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.877

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:

ZNF674 (HGNC:):

ZNF674 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ZNF674	NM_001190417.2 linkuse as main transcript	c.16-7G>A	splice_region_variant, intron_variant	ENST00000683375.1	NP_001177346.1	Q2M3X9A0A804HHU7
ZNF674	NM_001039891.3 linkuse as main transcript	c.16-7G>A	splice_region_variant, intron_variant		NP_001034980.1	Q2M3X9-1
ZNF674	NM_001146291.2 linkuse as main transcript	c.16-7G>A	splice_region_variant, intron_variant		NP_001139763.1	Q2M3X9-2
ZNF674	XM_011543943.4 linkuse as main transcript	c.16-7G>A	splice_region_variant, intron_variant		XP_011542245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF674	ENST00000683375.1 linkuse as main transcript	c.16-7G>A		splice_region_variant, intron_variant			NM_001190417.2	ENSP00000506769.1		A0A804HHU7

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

111658

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

33830

show subpopulations

Gnomad AFR

AF:

0.0000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000954

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000981

AC:

AN:

183463

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

67901

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000505

Gnomad SAS exome

AF:

0.000210

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000732

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000983

AC:

108

AN:

1098183

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

AN XY:

363567

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00152

Gnomad4 SAS exome

AF:

0.000314

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000380

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.000107

AC:

AN:

111709

Hom.:

Cov.:

AF XY:

0.0000590

AC XY:

AN XY:

33891

show subpopulations

Gnomad4 AFR

AF:

0.0000650

Gnomad4 AMR

AF:

0.0000953

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000374

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000756

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jun 12, 2013	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.33

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.026

SpliceAI score (max)

0.050

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