X-2488954-T-C

Position:

chrX-2488954-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001171136.2(ZBED1):c.1766A>G(p.Lys589Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000943 in 1,597,150 control chromosomes in the GnomAD database, including 12 homozygotes. There are 647 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Benignin ClinVar.

Frequency

Genomes: 𝑓 0.0053 ( 6 hom., 366 hem., cov: 33)

Exomes 𝑓: 0.00049 ( 6 hom. 281 hem. )

Consequence

ZBED1
NM_001171136.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.28

Variant links:

Genes affected

ZBED1 (HGNC:447): (zinc finger BED-type containing 1) This gene is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes. It was earlier identified as a gene with similarity to Ac transposable elements, however, was found not to have transposase activity. Later studies show that this gene product is localized in the nucleus and functions as a transcription factor. It binds to DNA elements found in the promoter regions of several genes related to cell proliferation, such as histone H1, hence may have a role in regulating genes related to cell proliferation. Alternatively spliced transcript variants with different 5' untranslated region have been found for this gene. [provided by RefSeq, Jan 2010]

ZBED1 links:

DHRSX (HGNC:18399): (dehydrogenase/reductase X-linked) Predicted to enable oxidoreductase activity. Involved in positive regulation of autophagy. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

DHRSX links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007619202).

BP6

Variant X-2488954-T-C is Benign according to our data. Variant chrX-2488954-T-C is described in ClinVar as [Benign]. Clinvar id is 784428.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00525 (800/152250) while in subpopulation AFR AF= 0.0182 (758/41550). AF 95% confidence interval is 0.0172. There are 6 homozygotes in gnomad4. There are 366 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZBED1	NM_001171136.2 linkuse as main transcript	c.1766A>G	p.Lys589Arg	missense_variant	2/2	ENST00000652001.1
DHRSX	NM_145177.3 linkuse as main transcript	c.109+11863A>G		intron_variant		ENST00000334651.11
ZBED1	NM_001171135.2 linkuse as main transcript	c.1766A>G	p.Lys589Arg	missense_variant	2/2
ZBED1	NM_004729.4 linkuse as main transcript	c.1766A>G	p.Lys589Arg	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBED1	ENST00000652001.1 linkuse as main transcript	c.1766A>G	p.Lys589Arg	missense_variant	2/2		NM_001171136.2	P1
DHRSX	ENST00000334651.11 linkuse as main transcript	c.109+11863A>G		intron_variant		1	NM_145177.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00523

AC:

796

AN:

152132

Hom.:

Cov.:

AF XY:

0.00487

AC XY:

362

AN XY:

74306

show subpopulations

Gnomad AFR

AF:

0.0182

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00153

AC:

364

AN:

237392

Hom.:

AF XY:

0.00110

AC XY:

140

AN XY:

127268

show subpopulations

Gnomad AFR exome

AF:

0.0204

Gnomad AMR exome

AF:

0.000773

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000735

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000932

Gnomad OTH exome

AF:

0.000870

GnomAD4 exome

AF:

0.000489

AC:

706

AN:

1444900

Hom.:

Cov.:

AF XY:

0.000392

AC XY:

281

AN XY:

716540

show subpopulations

Gnomad4 AFR exome

AF:

0.0183

Gnomad4 AMR exome

AF:

0.000754

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000363

Gnomad4 OTH exome

AF:

0.000890

GnomAD4 genome

AF:

0.00525

AC:

800

AN:

152250

Hom.:

Cov.:

AF XY:

0.00492

AC XY:

366

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0182

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00189

Bravo

AF:

0.00607

ESP6500AA

AF:

0.0188

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00169

AC:

205

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.92

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T;T

FATHMM_MKL

Benign

0.43

MetaRNN

Benign

0.0076

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.049

Sift

Benign

0.69

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.014

B;B;B

Vest4

0.13

MVP

0.067

MPC

0.36

ClinPred

0.0052

GERP RS

1.8

Varity_R

0.11

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