3-126461599-C-T

Variant names:

• chr3-126461599-C-T
• NM_025112.5:c.2063G>A

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.2063G>A​(p.Ser688Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: ZXDC NM_025112.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93
• 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=0.045833796).

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.2063G>A	p.Ser688Asn	missense	Exon 6 of 10	NP_079388.3
	ZXDC	NM_001040653.4		c.2063G>A	p.Ser688Asn	missense	Exon 6 of 6	NP_001035743.1	Q2QGD7-2
	ZXDC	NR_104249.2		n.2089G>A		non_coding_transcript_exon	Exon 6 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZXDC	ENST00000389709.8	TSL:1 MANE Select	c.2063G>A	p.Ser688Asn	missense	Exon 6 of 10	ENSP00000374359.3	Q2QGD7-1
	ZXDC	ENST00000336332.5	TSL:1	c.2063G>A	p.Ser688Asn	missense	Exon 6 of 6	ENSP00000337694.5	Q2QGD7-2
	ZXDC	ENST00000515545.5	TSL:1	n.1184G>A		non_coding_transcript_exon	Exon 6 of 9	ENSP00000426532.1	H0YAA9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.087
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.90
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.54
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.9
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.33	N
REVEL	Benign	0.033
Sift	Benign	0.71	T
Sift4G	Benign	0.53	T
Polyphen		0.0060	B
Vest4		0.066
MutPred		0.16		Loss of loop (P = 0.0128)
MVP		0.048
MPC		0.083
ClinPred		0.099	T
GERP RS		4.0
Varity_R		0.019
gMVP		0.11
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chr3-126180442;