rs868654990

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-137566745-C-A
• chrX-137566745-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003413.4(ZIC3):​c.54C>A​(p.Ser18Arg) variant causes a missense 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S18S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 25)
• Consequence: ZIC3 NM_003413.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1558317).

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>A	p.Ser18Arg	missense	Exon 1 of 3	NP_003404.1	O60481-1
	ZIC3	NM_001330661.1		c.54C>A	p.Ser18Arg	missense	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>A	p.Ser18Arg	missense	Exon 1 of 3	ENSP00000287538.5	O60481-1
	ZIC3	ENST00000919832.1		c.54C>A	p.Ser18Arg	missense	Exon 4 of 6	ENSP00000589891.1
	ZIC3	ENST00000919833.1		c.54C>A	p.Ser18Arg	missense	Exon 4 of 6	ENSP00000589892.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 25

Alfa AF: 0.00104 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.79
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.067
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.34	T
Polyphen		0.17	B
Vest4		0.38
MutPred		0.21		Gain of methylation at S18 (P = 0.0121)
MVP		0.12
MPC		1.5
ClinPred		0.41	T
GERP RS		3.2
PromoterAI		0.0081	Neutral
Varity_R		0.57
gMVP		0.64
Mutation Taster		=82/18	polymorphism

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;