chrX-137566745-C-T

Variant names:

• chrX-137566745-C-T
• rs868654990
• NM_003413.4:c.54C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_003413.4(ZIC3):​c.54C>T​(p.Ser18Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ZIC3 NM_003413.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.794
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant X-137566745-C-T is Benign according to our data. Variant chrX-137566745-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2012571.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.794 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003413.4. 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
	ZIC3	NM_003413.4	MANE Select	c.54C>T	p.Ser18Ser	synonymous	Exon 1 of 3	NP_003404.1	O60481-1
	ZIC3	NM_001330661.1		c.54C>T	p.Ser18Ser	synonymous	Exon 1 of 3	NP_001317590.1	O60481-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIC3	ENST00000287538.10	TSL:1 MANE Select	c.54C>T	p.Ser18Ser	synonymous	Exon 1 of 3	ENSP00000287538.5	O60481-1
	ZIC3	ENST00000919832.1		c.54C>T	p.Ser18Ser	synonymous	Exon 4 of 6	ENSP00000589891.1
	ZIC3	ENST00000919833.1		c.54C>T	p.Ser18Ser	synonymous	Exon 4 of 6	ENSP00000589892.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1076344 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 349574

African (AFR) AF: 0.00 AC: 0 AN: 26118

American (AMR) AF: 0.00 AC: 0 AN: 32702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18986

East Asian (EAS) AF: 0.00 AC: 0 AN: 29324

South Asian (SAS) AF: 0.00 AC: 0 AN: 51429

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36055

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3957

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 832519

Other (OTH) AF: 0.00 AC: 0 AN: 45254

GnomAD4 genome Cov.: 25

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Heterotaxy, visceral, 1, X-linked (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		0.79
PromoterAI		-0.014	Neutral

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: rs868654990; hg19: chrX-136648904;