chr3-126439712-C-T

Variant names:

• chr3-126439712-C-T
• rs932318489
• NM_025112.5:c.2410G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_025112.5(ZXDC):​c.2410G>A​(p.Glu804Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000451 in 1,551,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: ZXDC NM_025112.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28259277).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025112.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZXDC	NM_025112.5	MANE Select	c.2410G>A	p.Glu804Lys	missense	Exon 9 of 10	NP_079388.3
	ZXDC	NR_104249.2		n.2616G>A		non_coding_transcript_exon	Exon 8 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZXDC	ENST00000389709.8	TSL:1 MANE Select	c.2410G>A	p.Glu804Lys	missense	Exon 9 of 10	ENSP00000374359.3	Q2QGD7-1
	ZXDC	ENST00000514463.1	TSL:1	n.3698G>A		non_coding_transcript_exon	Exon 1 of 2
	ZXDC	ENST00000515545.5	TSL:1	n.*457G>A		non_coding_transcript_exon	Exon 8 of 9	ENSP00000426532.1	H0YAA9

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000194 AC: 3 AN: 154370 AF XY: 0.0000245

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000905

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000166

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1399322 Hom.: 0 Cov.: 30 AF XY: 0.00000580 AC XY: 4 AN XY: 690234

African (AFR) AF: 0.00 AC: 0 AN: 31672

American (AMR) AF: 0.00 AC: 0 AN: 35752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25154

East Asian (EAS) AF: 0.00 AC: 0 AN: 35866

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00000463 AC: 5 AN: 1079112

Other (OTH) AF: 0.00 AC: 0 AN: 58016

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74360

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.4
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.081
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.92	P
Vest4		0.47
MutPred		0.17		Gain of ubiquitination at E804 (P = 0.0042)
MVP		0.22
MPC		0.22
ClinPred		0.49	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.24
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs932318489; hg19: chr3-126158555;