rs812368

chr3-126456558-G-A

Variant summary

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

The NM_025112.5(ZXDC):c.2212+3095C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,122 control chromosomes in the GnomAD database, including 28,713 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 (28713 hom., cov: 33)
• Consequence: ZXDC NM_025112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725

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 (SAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZXDC	NM_025112.5	c.2212+3095C>T		intron_variant		ENST00000389709.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZXDC	ENST00000389709.8	c.2212+3095C>T		intron_variant		1	NM_025112.5	P2
ZXDC	ENST00000515545.5	c.*259+4712C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92509 AN: 152004 Hom.: 28690 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.609 AC: 92568 AN: 152122 Hom.: 28713 Cov.: 33 AF XY: 0.608 AC XY: 45238 AN XY: 74366

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.622

Alfa AF: 0.663 Hom.: 68043

Bravo AF: 0.598

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	-0.93
Cadd	Benign	0.48
Dann	Benign	0.33

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: rs812368; hg19: chr3-126175401;