3-126470157-C-A

Position:

• chr3-126470157-C-A

Variant summary

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

The NM_025112.5(ZXDC):​c.1270+738G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,058 control chromosomes in the GnomAD database, including 21,241 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 0.50 (21241 hom., cov: 33)
• Consequence: ZXDC NM_025112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZXDC	NM_025112.5	c.1270+738G>T		intron_variant		ENST00000389709.8	NP_079388.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZXDC	ENST00000389709.8	c.1270+738G>T		intron_variant		1	NM_025112.5	ENSP00000374359	P2
ZXDC	ENST00000336332.5	c.1270+738G>T		intron_variant		1		ENSP00000337694	A2
ZXDC	ENST00000515545.5	c.392+738G>T		intron_variant, NMD_transcript_variant		1		ENSP00000426532

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76460 AN: 151940 Hom.: 21238 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.524

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.503 AC: 76471 AN: 152058 Hom.: 21241 Cov.: 33 AF XY: 0.503 AC XY: 37372 AN XY: 74324

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.520

Alfa AF: 0.590 Hom.: 12407

Bravo AF: 0.491

Asia WGS AF: 0.443 AC: 1540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.37
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs777498; hg19: chr3-126189000;