chr3-126470157-C-A

Variant names:

• chr3-126470157-C-A
• rs777498
• NM_025112.5:c.1270+738G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZXDC	NM_025112.5	c.1270+738G>T		intron_variant	Intron 4 of 9	ENST00000389709.8	NP_079388.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZXDC	ENST00000389709.8	c.1270+738G>T		intron_variant	Intron 4 of 9	1	NM_025112.5	ENSP00000374359.3
ZXDC	ENST00000336332.5	c.1270+738G>T		intron_variant	Intron 4 of 5	1		ENSP00000337694.5
ZXDC	ENST00000515545.5	n.391+738G>T		intron_variant	Intron 4 of 8	1		ENSP00000426532.1

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

African (AFR) AF: 0.250 AC: 10373 AN: 41496

American (AMR) AF: 0.544 AC: 8299 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2023 AN: 3472

East Asian (EAS) AF: 0.490 AC: 2524 AN: 5152

South Asian (SAS) AF: 0.553 AC: 2664 AN: 4820

European-Finnish (FIN) AF: 0.598 AC: 6312 AN: 10560

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42280 AN: 67978

Other (OTH) AF: 0.520 AC: 1096 AN: 2108

Alfa AF: 0.589 Hom.: 13860

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
PhyloP100		-1.2
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs777498; hg19: chr3-126189000;