rs1933696392

Variant names:

• chr3-126441912-T-A
• rs1933696392
• NM_025112.5:c.2247A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025112.5(ZXDC):​c.2247A>T​(p.Glu749Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZXDC NM_025112.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00900
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.016753525).

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.2247A>T	p.Glu749Asp	missense	Exon 8 of 10	NP_079388.3
	ZXDC	NR_104249.2		n.2453A>T		non_coding_transcript_exon	Exon 7 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZXDC	ENST00000389709.8	TSL:1 MANE Select	c.2247A>T	p.Glu749Asp	missense	Exon 8 of 10	ENSP00000374359.3	Q2QGD7-1
	ZXDC	ENST00000514463.1	TSL:1	n.1498A>T		non_coding_transcript_exon	Exon 1 of 2
	ZXDC	ENST00000515545.5	TSL:1	n.*294A>T		non_coding_transcript_exon	Exon 7 of 9	ENSP00000426532.1	H0YAA9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1458904 Hom.: 0 Cov.: 34 AF XY: 0.00000276 AC XY: 2 AN XY: 725744

African (AFR) AF: 0.00 AC: 0 AN: 33296

American (AMR) AF: 0.00 AC: 0 AN: 43988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 85770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110848

Other (OTH) AF: 0.00 AC: 0 AN: 60274

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	0.067
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.74
DANN	Benign	0.93
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00088	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.90	N
PhyloP100		0.0090
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.045
Sift	Benign	0.48	T
Sift4G	Benign	0.79	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.068		Loss of methylation at K748 (P = 0.0814)
MVP		0.030
MPC		0.079
ClinPred		0.063	T
GERP RS		-0.25
Varity_R		0.046
gMVP		0.039
Mutation Taster		=93/7	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: rs1933696392; hg19: chr3-126160755;