rs772644610

Variant names:

• chrX-65502454-C-T
• rs772644610
• NM_001010888.4:c.1756C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001010888.4(ZC3H12B):​c.1756C>T​(p.Arg586Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000877 in 1,208,885 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 41 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., 4 hem., cov: 22)
  • Exomes 𝑓: 0.000084 (0 hom. 37 hem.)
• Consequence: ZC3H12B NM_001010888.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.512
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014586955).
• BS2: High AC in GnomAd4 at 14 AD gene.

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.1756C>T	p.Arg586Cys	missense	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.1756C>T	p.Arg586Cys	missense	Exon 10 of 10	ENSP00000340839.4	Q5HYM0-1
	ZC3H12B	ENST00000888353.1		c.1756C>T	p.Arg586Cys	missense	Exon 8 of 8	ENSP00000558412.1
	ZC3H12B	ENST00000916775.1		c.1756C>T	p.Arg586Cys	missense	Exon 8 of 8	ENSP00000586834.1

Frequencies

GnomAD3 genomes AF: 0.000126 AC: 14 AN: 111148 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000573

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.0000943

Gnomad OTH AF: 0.000674

GnomAD2 exomes AF: 0.0000723 AC: 13 AN: 179821 AF XY: 0.000106

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000838 AC: 92 AN: 1097688 Hom.: 0 Cov.: 31 AF XY: 0.000102 AC XY: 37 AN XY: 363122

African (AFR) AF: 0.000114 AC: 3 AN: 26400

American (AMR) AF: 0.000142 AC: 5 AN: 35172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19375

East Asian (EAS) AF: 0.00 AC: 0 AN: 30196

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40503

Middle Eastern (MID) AF: 0.00121 AC: 5 AN: 4136

European-Non Finnish (NFE) AF: 0.0000867 AC: 73 AN: 841829

Other (OTH) AF: 0.000109 AC: 5 AN: 46073

GnomAD4 genome AF: 0.000126 AC: 14 AN: 111197 Hom.: 0 Cov.: 22 AF XY: 0.000120 AC XY: 4 AN XY: 33403

African (AFR) AF: 0.0000327 AC: 1 AN: 30585

American (AMR) AF: 0.000572 AC: 6 AN: 10493

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3522

South Asian (SAS) AF: 0.00 AC: 0 AN: 2545

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6001

Middle Eastern (MID) AF: 0.00459 AC: 1 AN: 218

European-Non Finnish (NFE) AF: 0.0000943 AC: 5 AN: 53005

Other (OTH) AF: 0.000665 AC: 1 AN: 1503

Alfa AF: 0.000356 Hom.: 2

Bravo AF: 0.000253

ExAC AF: 0.000107 AC: 13

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	Benign	0.076
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	14
DANN	Benign	0.89
DEOGEN2	Benign	0.0018	T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N
PhyloP100		0.51
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.035
Sift	Benign	0.28	T
Sift4G	Benign	0.11	T
Vest4		0.043
MVP		0.043
MPC		0.68
ClinPred		0.016	T
GERP RS		3.3
Varity_R		0.13
gMVP		0.15
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs772644610; hg19: chrX-64722334; COSMIC: COSV59050543; COSMIC: COSV59050543;