rs7064929

Variant names:

• chrX-65147139-G-A
• rs7064929
• NM_001010888.4:c.-568+71227G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010888.4(ZC3H12B):​c.-568+71227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 111,530 control chromosomes in the GnomAD database, including 7,619 homozygotes. There are 7,417 hemizygotes in GnomAD. 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 0.24 (7619 hom., 7417 hem., cov: 23)
• Consequence: ZC3H12B NM_001010888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• Publications: 5 publications found

Genes affected

ZC3H12B (HGNC:17407): (zinc finger CCCH-type containing 12B) The protein encoded by this gene belongs to a family of CCCH-type zinc finger proteins that are involved in the proinflammatory activation of macrophages. The exact function of this family member is unknown, but it is thought to function as a ribonuclease. [provided by RefSeq, May 2010]

ZC3H12B Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H12B	NM_001010888.4	c.-568+71227G>A		intron_variant	Intron 2 of 9	ENST00000338957.5	NP_001010888.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H12B	ENST00000338957.5	c.-568+71227G>A		intron_variant	Intron 2 of 9	1	NM_001010888.4	ENSP00000340839.4
ZC3H12B	ENST00000696368.1	c.-313+71227G>A		intron_variant	Intron 2 of 8			ENSP00000512583.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 26660 AN: 111474 Hom.: 7612 Cov.: 23

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.00603

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.0289

Gnomad FIN AF: 0.00247

Gnomad MID AF: 0.0544

Gnomad NFE AF: 0.00651

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.240 AC: 26731 AN: 111530 Hom.: 7619 Cov.: 23 AF XY: 0.220 AC XY: 7417 AN XY: 33776

African (AFR) AF: 0.824 AC: 25078 AN: 30428

American (AMR) AF: 0.0873 AC: 919 AN: 10530

Ashkenazi Jewish (ASJ) AF: 0.00603 AC: 16 AN: 2654

East Asian (EAS) AF: 0.000282 AC: 1 AN: 3545

South Asian (SAS) AF: 0.0289 AC: 78 AN: 2696

European-Finnish (FIN) AF: 0.00247 AC: 15 AN: 6083

Middle Eastern (MID) AF: 0.0596 AC: 13 AN: 218

European-Non Finnish (NFE) AF: 0.00651 AC: 346 AN: 53174

Other (OTH) AF: 0.175 AC: 265 AN: 1517

Alfa AF: 0.0954 Hom.: 10890

Bravo AF: 0.272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.97
DANN	Benign	0.62
PhyloP100		-0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7064929; hg19: chrX-64367019;