X-65414981-C-T

Variant names:

• chrX-65414981-C-T
• rs7884174
• NM_001010888.4:c.-157+16277C>T

Variant summary

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

The NM_001010888.4(ZC3H12B):​c.-157+16277C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 111,604 control chromosomes in the GnomAD database, including 2,738 homozygotes. There are 4,421 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 0.14 (2738 hom., 4421 hem., cov: 23)
• Consequence: ZC3H12B NM_001010888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H12B	NM_001010888.4	c.-157+16277C>T		intron_variant	Intron 5 of 9	ENST00000338957.5	NP_001010888.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H12B	ENST00000338957.5	c.-157+16277C>T		intron_variant	Intron 5 of 9	1	NM_001010888.4	ENSP00000340839.4
ZC3H12B	ENST00000696368.1	c.-252+16328C>T		intron_variant	Intron 3 of 8			ENSP00000512583.1
ZC3H12B	ENST00000617377.1	n.407+16277C>T		intron_variant	Intron 3 of 5	5

Frequencies

GnomAD3 genomes AF: 0.143 AC: 15980 AN: 111551 Hom.: 2730 Cov.: 23

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.00528

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0262

Gnomad FIN AF: 0.00247

Gnomad MID AF: 0.0424

Gnomad NFE AF: 0.00589

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.144 AC: 16032 AN: 111604 Hom.: 2738 Cov.: 23 AF XY: 0.131 AC XY: 4421 AN XY: 33854

African (AFR) AF: 0.489 AC: 14906 AN: 30512

American (AMR) AF: 0.0513 AC: 542 AN: 10571

Ashkenazi Jewish (ASJ) AF: 0.00528 AC: 14 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3560

South Asian (SAS) AF: 0.0263 AC: 70 AN: 2663

European-Finnish (FIN) AF: 0.00247 AC: 15 AN: 6063

Middle Eastern (MID) AF: 0.0465 AC: 10 AN: 215

European-Non Finnish (NFE) AF: 0.00589 AC: 313 AN: 53160

Other (OTH) AF: 0.106 AC: 162 AN: 1523

Alfa AF: 0.0297 Hom.: 477

Bravo AF: 0.163

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.69
PhyloP100		0.23

Splicing

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

Other links and lift over

dbSNP: rs7884174; hg19: chrX-64634861;