X-137567340-C-T

Variant names:

• chrX-137567340-C-T
• NM_003413.4:c.649C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_003413.4(ZIC3):​c.649C>T​(p.Pro217Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,687 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000018 (0 hom. 2 hem.)
• Consequence: ZIC3 NM_003413.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.97

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16606942).
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC3	NM_003413.4	c.649C>T	p.Pro217Ser	missense_variant	Exon 1 of 3	ENST00000287538.10	NP_003404.1
ZIC3	NM_001330661.1	c.649C>T	p.Pro217Ser	missense_variant	Exon 1 of 3		NP_001317590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZIC3	ENST00000287538.10	c.649C>T	p.Pro217Ser	missense_variant	Exon 1 of 3	1	NM_003413.4	ENSP00000287538.5
ZIC3	ENST00000370606.3	c.649C>T	p.Pro217Ser	missense_variant	Exon 1 of 3	5		ENSP00000359638.3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097687 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 2 AN XY: 363377

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000516

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.66	N;N
REVEL	Benign	0.093
Sift	Benign	0.037	D;D
Sift4G	Benign	0.40	T;T
Polyphen		0.0	B;.
Vest4		0.16
MutPred		0.32		Gain of glycosylation at P217 (P = 0.1228);Gain of glycosylation at P217 (P = 0.1228);
MVP		0.21
MPC		1.3
ClinPred		0.85	D
GERP RS		3.7
Varity_R		0.094
gMVP		0.34

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-136649499;