X-137565967-C-T

Variant names:

• chrX-137565967-C-T
• rs12843772
• NM_003413.4:c.-725C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_003413.4(ZIC3):​c.-725C>T variant causes a upstream gene 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 NM_003413.4 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.172

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC3	NM_003413.4	c.-725C>T		upstream_gene_variant		ENST00000287538.10	NP_003404.1
ZIC3	NM_001330661.1	c.-725C>T		upstream_gene_variant			NP_001317590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZIC3	ENST00000287538.10	c.-725C>T		upstream_gene_variant		1	NM_003413.4	ENSP00000287538.5

Frequencies

GnomAD3 genomes AF: 0.413 AC: 46036 AN: 111600 Hom.: 7259 Cov.: 24 AF XY: 0.416 AC XY: 14111 AN XY: 33898

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

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.410

Alfa AF: 0.460 Hom.: 3295

Bravo AF: 0.400

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 17, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	16
DANN	Uncertain	0.99

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12843772; hg19: chrX-136648126;