X-57592067-C-T

Variant summary

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

The NM_007157.4(ZXDB):​c.19C>T​(p.Leu7Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,034,637 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.000012 ( 0 hom. 2 hem. )

Consequence

ZXDB
NM_007157.4 missense

Scores

1
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0420
Variant links:
Genes affected
ZXDB (HGNC:13199): (zinc finger X-linked duplicated B) The ZXDB gene is one of a pair of duplicated zinc finger genes on chromosome Xp11.21 (Greig et al., 1993 [PubMed 8268913]); see also ZXDA (MIM 300235).[supplied by OMIM, Jul 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06766325).
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZXDBNM_007157.4 linkc.19C>T p.Leu7Phe missense_variant Exon 1 of 1 ENST00000374888.3 NP_009088.1 P98169

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZXDBENST00000374888.3 linkc.19C>T p.Leu7Phe missense_variant Exon 1 of 1 6 NM_007157.4 ENSP00000364023.1 P98169

Frequencies

GnomAD3 genomes
AF:
0.0000269
AC:
3
AN:
111537
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33739
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000854
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
GnomAD4 exome
AF:
0.0000119
AC:
11
AN:
923058
Hom.:
0
Cov.:
28
AF XY:
0.00000696
AC XY:
2
AN XY:
287558
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000383
Gnomad4 SAS exome
AF:
0.0000321
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000132
Gnomad4 OTH exome
AF:
0.0000261
GnomAD4 genome
AF:
0.0000269
AC:
3
AN:
111579
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33791
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000858
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 13, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.19C>T (p.L7F) alteration is located in exon 1 (coding exon 1) of the ZXDB gene. This alteration results from a C to T substitution at nucleotide position 19, causing the leucine (L) at amino acid position 7 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.099
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.034
T
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.60
T
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.068
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.056
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0090
D
Polyphen
0.0010
B
Vest4
0.071
MutPred
0.14
Gain of methylation at K5 (P = 0.0601);
MVP
0.22
MPC
2.3
ClinPred
0.92
D
GERP RS
0.63
Varity_R
0.43
gMVP
0.065

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.

Other links and lift over

dbSNP: rs1218118242; hg19: chrX-57618500; API