chrX-65489127-A-G

Variant names:

• chrX-65489127-A-G
• rs192520287
• NM_001010888.4:c.326A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001010888.4(ZC3H12B):​c.326A>G​(p.Gln109Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000515 in 1,210,315 control chromosomes in the GnomAD database, including 5 homozygotes. There are 170 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00055 (0 hom., 25 hem., cov: 22)
  • Exomes 𝑓: 0.00051 (5 hom. 145 hem.)
• Consequence: ZC3H12B NM_001010888.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.57
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0068853796).
• BP6: Variant X-65489127-A-G is Benign according to our data. Variant chrX-65489127-A-G is described in ClinVar as Benign. ClinVar VariationId is 719851.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 62 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.326A>G	p.Gln109Arg	missense	Exon 6 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.326A>G	p.Gln109Arg	missense	Exon 6 of 10	ENSP00000340839.4	Q5HYM0-1
	ZC3H12B	ENST00000888353.1		c.326A>G	p.Gln109Arg	missense	Exon 4 of 8	ENSP00000558412.1
	ZC3H12B	ENST00000916775.1		c.326A>G	p.Gln109Arg	missense	Exon 4 of 8	ENSP00000586834.1

Frequencies

GnomAD3 genomes AF: 0.000562 AC: 63 AN: 112135 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00586

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00281 AC: 509 AN: 181379 AF XY: 0.00194

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0185

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000674

GnomAD4 exome AF: 0.000511 AC: 561 AN: 1098124 Hom.: 5 Cov.: 31 AF XY: 0.000399 AC XY: 145 AN XY: 363550

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.0157 AC: 551 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54149

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40520

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842035

Other (OTH) AF: 0.000217 AC: 10 AN: 46081

GnomAD4 genome AF: 0.000553 AC: 62 AN: 112191 Hom.: 0 Cov.: 22 AF XY: 0.000728 AC XY: 25 AN XY: 34359

African (AFR) AF: 0.0000323 AC: 1 AN: 30947

American (AMR) AF: 0.00576 AC: 61 AN: 10599

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3573

South Asian (SAS) AF: 0.00 AC: 0 AN: 2679

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53233

Other (OTH) AF: 0.00 AC: 0 AN: 1536

Alfa AF: 0.00108 Hom.: 16

Bravo AF: 0.00133

ExAC AF: 0.00223 AC: 270

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0069	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		8.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.12
Sift	Benign	0.037	D
Sift4G	Benign	0.17	T
Vest4		0.74
MVP		0.068
MPC		1.5
ClinPred		0.15	T
GERP RS		4.2
PromoterAI		0.00090	Neutral
Varity_R		0.21
gMVP		0.35
Mutation Taster		=99/1	polymorphism (auto)

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: rs192520287; hg19: chrX-64709007;