X-65502568-C-T

Variant names:

• chrX-65502568-C-T
• rs753303498
• NM_001010888.4:c.1870C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001010888.4(ZC3H12B):​c.1870C>T​(p.Arg624*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,245 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: ZC3H12B NM_001010888.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• Publications: 0 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]

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]

LAS1L Gene-Disease associations (from GenCC):

• Wilson-Turner syndrome

  Inheritance: XL Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• spinal muscular atrophy with respiratory distress type 2

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010888.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H12B	NM_001010888.4	MANE Select	c.1870C>T	p.Arg624*	stop_gained	Exon 10 of 10	NP_001010888.3	Q5HYM0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H12B	ENST00000338957.5	TSL:1 MANE Select	c.1870C>T	p.Arg624*	stop_gained	Exon 10 of 10	ENSP00000340839.4	Q5HYM0-1
	ZC3H12B	ENST00000888353.1		c.1870C>T	p.Arg624*	stop_gained	Exon 8 of 8	ENSP00000558412.1
	ZC3H12B	ENST00000916775.1		c.1870C>T	p.Arg624*	stop_gained	Exon 8 of 8	ENSP00000586834.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097245 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 362697

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.00 AC: 0 AN: 35130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19367

East Asian (EAS) AF: 0.00 AC: 0 AN: 30176

South Asian (SAS) AF: 0.00 AC: 0 AN: 53875

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841666

Other (OTH) AF: 0.00 AC: 0 AN: 46053

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	35
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.80	D
PhyloP100		2.9
Vest4		0.081
GERP RS		3.3
Mutation Taster		=17/183	disease causing

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

Other links and lift over

dbSNP: rs753303498; hg19: chrX-64722448;