X-65499201-G-T

Variant names:

• chrX-65499201-G-T
• NM_001010888.4:c.951G>T

Variant summary

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

The NM_001010888.4(ZC3H12B):​c.951G>T​(p.Glu317Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZC3H12B NM_001010888.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38
• 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.951G>T	p.Glu317Asp	missense	Exon 8 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.951G>T	p.Glu317Asp	missense	Exon 8 of 10	ENSP00000340839.4	Q5HYM0-1
	ZC3H12B	ENST00000888353.1		c.951G>T	p.Glu317Asp	missense	Exon 6 of 8	ENSP00000558412.1
	ZC3H12B	ENST00000916775.1		c.951G>T	p.Glu317Asp	missense	Exon 6 of 8	ENSP00000586834.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0090	D
Vest4		0.71
MVP		0.15
MPC		1.3
ClinPred		0.97	D
GERP RS		2.3
Varity_R		0.72
gMVP		0.74
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chrX-64719081;