X-65502090-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001010888.4(ZC3H12B):c.1392G>A(p.Ser464=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000323 in 1,209,184 control chromosomes in the GnomAD database, including 1 homozygotes. There are 120 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., 56 hem., cov: 22)
  • Exomes 𝑓: 0.00019 (1 hom. 64 hem.)
• Consequence: ZC3H12B NM_001010888.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.399

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]

LAS1L (HGNC:25726): (LAS1 like ribosome biogenesis factor) Enables RNA binding activity. Predicted to be involved in maturation of 5.8S rRNA and maturation of LSU-rRNA. Located in membrane. Part of MLL1 complex. Implicated in Wilson-Turner syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant X-65502090-G-A is Benign according to our data. Variant chrX-65502090-G-A is described in ClinVar as [Benign]. Clinvar id is 718702.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 56 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H12B	NM_001010888.4	c.1392G>A	p.Ser464=	synonymous_variant	10/10	ENST00000338957.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZC3H12B	ENST00000338957.5	c.1392G>A	p.Ser464=	synonymous_variant	10/10	1	NM_001010888.4	P1

Frequencies

GnomAD3 genomes AF: 0.00166 AC: 185 AN: 111280 Hom.: 0 Cov.: 22 AF XY: 0.00167 AC XY: 56 AN XY: 33502

Gnomad AFR AF: 0.00563

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000956

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000189

Gnomad OTH AF: 0.00133

GnomAD3 exomes AF: 0.000504 AC: 91 AN: 180549 Hom.: 1 AF XY: 0.000285 AC XY: 19 AN XY: 66599

Gnomad AFR exome AF: 0.00678

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000372

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000187 AC: 205 AN: 1097851 Hom.: 1 Cov.: 31 AF XY: 0.000176 AC XY: 64 AN XY: 363291

Gnomad4 AFR exome AF: 0.00583

Gnomad4 AMR exome AF: 0.000256

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000261

Gnomad4 OTH exome AF: 0.000391

GnomAD4 genome AF: 0.00167 AC: 186 AN: 111333 Hom.: 0 Cov.: 22 AF XY: 0.00167 AC XY: 56 AN XY: 33565

Gnomad4 AFR AF: 0.00565

Gnomad4 AMR AF: 0.000955

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000189

Gnomad4 OTH AF: 0.00131

Alfa AF: 0.000955 Hom.: 7

Bravo AF: 0.00206

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	3.5
Dann	Benign	0.81

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: rs191189996; hg19: chrX-64721970; COSMIC: COSV59048691; COSMIC: COSV59048691;