rs12843772

Variant names:

• chrX-137565967-C-T
• rs12843772
• ENST00000919832.1:c.-171+282C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The ENST00000919832.1(ZIC3):​c.-171+282C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 111,641 control chromosomes in the GnomAD database, including 7,251 homozygotes. There are 14,114 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.41 (7251 hom., 14114 hem., cov: 24)
• Consequence: ZIC3 ENST00000919832.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.172
• Publications: 3 publications found

Genes affected

ZIC3 (HGNC:12874): (Zic family member 3) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This nuclear protein probably functions as a transcription factor in early stages of left-right body axis formation. Mutations in this gene cause X-linked visceral heterotaxy, which includes congenital heart disease and left-right axis defects in organs. [provided by RefSeq, Jul 2008]

LINC02931 (HGNC:55853): (long intergenic non-protein coding RNA 2931)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant X-137565967-C-T is Benign according to our data. Variant chrX-137565967-C-T is described in ClinVar as Benign. ClinVar VariationId is 1239042.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000919832.1. 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
	ZIC3	NM_003413.4	MANE Select	c.-725C>T		upstream_gene	N/A	NP_003404.1	O60481-1
	ZIC3	NM_001330661.1		c.-725C>T		upstream_gene	N/A	NP_001317590.1	O60481-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIC3	ENST00000919832.1		c.-171+282C>T		intron	N/A	ENSP00000589891.1
	ZIC3	ENST00000919833.1		c.-171+279C>T		intron	N/A	ENSP00000589892.1
	ZIC3	ENST00000919834.1		c.-171+282C>T		intron	N/A	ENSP00000589893.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 46036 AN: 111600 Hom.: 7259 Cov.: 24

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.415

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.412 AC: 46022 AN: 111641 Hom.: 7251 Cov.: 24 AF XY: 0.416 AC XY: 14114 AN XY: 33949

African (AFR) AF: 0.210 AC: 6514 AN: 30983

American (AMR) AF: 0.498 AC: 5378 AN: 10791

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1014 AN: 2637

East Asian (EAS) AF: 0.395 AC: 1356 AN: 3432

South Asian (SAS) AF: 0.492 AC: 1334 AN: 2714

European-Finnish (FIN) AF: 0.487 AC: 2924 AN: 6010

Middle Eastern (MID) AF: 0.372 AC: 80 AN: 215

European-Non Finnish (NFE) AF: 0.503 AC: 26470 AN: 52669

Other (OTH) AF: 0.410 AC: 628 AN: 1533

Alfa AF: 0.460 Hom.: 3295

Bravo AF: 0.400

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
BayesDel_noAF	Benign	-0.24
CADD	Benign	16
DANN	Uncertain	0.99
PhyloP100		-0.17
PromoterAI		0.036	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12843772; hg19: chrX-136648126;