chr3-126471076-A-G

Position:

• chr3-126471076-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025112.5(ZXDC):​c.1140-51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,586,982 control chromosomes in the GnomAD database, including 360,225 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (28945 hom., cov: 33)
  • Exomes 𝑓: 0.68 (331280 hom.)
• Consequence: ZXDC NM_025112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZXDC	NM_025112.5	c.1140-51T>C		intron_variant		ENST00000389709.8	NP_079388.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZXDC	ENST00000389709.8	c.1140-51T>C		intron_variant		1	NM_025112.5	ENSP00000374359	P2
ZXDC	ENST00000336332.5	c.1140-51T>C		intron_variant		1		ENSP00000337694	A2
ZXDC	ENST00000515545.5	c.262-51T>C		intron_variant, NMD_transcript_variant		1		ENSP00000426532

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92885 AN: 152028 Hom.: 28922 Cov.: 33

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.622

GnomAD3 exomes AF: 0.653 AC: 151149 AN: 231500 Hom.: 49516 AF XY: 0.666 AC XY: 83938 AN XY: 126050

Gnomad AFR exome AF: 0.483

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.642

Gnomad EAS exome AF: 0.574

Gnomad SAS exome AF: 0.757

Gnomad FIN exome AF: 0.653

Gnomad NFE exome AF: 0.681

Gnomad OTH exome AF: 0.647

GnomAD4 exome AF: 0.678 AC: 972377 AN: 1434836 Hom.: 331280 Cov.: 30 AF XY: 0.682 AC XY: 484409 AN XY: 710390

Gnomad4 AFR exome AF: 0.470

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.643

Gnomad4 EAS exome AF: 0.535

Gnomad4 SAS exome AF: 0.756

Gnomad4 FIN exome AF: 0.650

Gnomad4 NFE exome AF: 0.689

Gnomad4 OTH exome AF: 0.663

GnomAD4 genome AF: 0.611 AC: 92944 AN: 152146 Hom.: 28945 Cov.: 33 AF XY: 0.611 AC XY: 45425 AN XY: 74388

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.623

Alfa AF: 0.661 Hom.: 17222

Bravo AF: 0.601

Asia WGS AF: 0.611 AC: 2127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs777499; hg19: chr3-126189919; COSMIC: COSV60446056;