3-126459671-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025112.5(ZXDC):​c.2194G>A​(p.Gly732Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZXDC
NM_025112.5 missense

Scores

5
3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.47
Variant links:
Genes affected
ZXDC (HGNC:28160): (ZXD family zinc finger C) Enables C2H2 zinc finger domain binding activity; LRR domain binding activity; and transcription coactivator activity. Involved in positive regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZXDCNM_025112.5 linkc.2194G>A p.Gly732Arg missense_variant Exon 7 of 10 ENST00000389709.8 NP_079388.3 Q2QGD7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZXDCENST00000389709.8 linkc.2194G>A p.Gly732Arg missense_variant Exon 7 of 10 1 NM_025112.5 ENSP00000374359.3 Q2QGD7-1
ZXDCENST00000515545.5 linkn.*259+1599G>A intron_variant Intron 6 of 8 1 ENSP00000426532.1 H0YAA9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461886
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.00000827
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 12, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2194G>A (p.G732R) alteration is located in exon 7 (coding exon 7) of the ZXDC gene. This alteration results from a G to A substitution at nucleotide position 2194, causing the glycine (G) at amino acid position 732 to be replaced by an arginine (R). 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
0.23
BayesDel_addAF
Benign
-0.055
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.12
T
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.048
D
MetaRNN
Uncertain
0.66
D
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.43
T
PROVEAN
Uncertain
-2.5
D
REVEL
Benign
0.23
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.14
T
Polyphen
1.0
D
Vest4
0.75
MutPred
0.20
Gain of methylation at K729 (P = 0.051);
MVP
0.43
MPC
0.23
ClinPred
0.97
D
GERP RS
5.6
Varity_R
0.64
gMVP
0.23

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: rs773536066; hg19: chr3-126178514; API