3-147390969-C-T

Variant names:

• chr3-147390969-C-T
• NM_032153.6:c.966G>A
• ZIC4 p.Ser322Ser

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_032153.6(ZIC4):​c.966G>A​(p.Ser322Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S322S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZIC4 NM_032153.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690
• Publications: 0 publications found

Genes affected

ZIC4 (HGNC:20393): (Zic family member 4) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. Members of this family are important during development, and have been associated with X-linked visceral heterotaxy and holoprosencephaly type 5. This gene is closely linked to the gene encoding zinc finger protein of the cerebellum 1, a related family member on chromosome 3. Heterozygous deletion of these linked genes is involved in Dandy-Walker malformation, which is a congenital cerebellar malformation. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=-0.69 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032153.6. 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
	ZIC4	NM_032153.6	MANE Select	c.966G>A	p.Ser322Ser	synonymous	Exon 4 of 5	NP_115529.2
	ZIC4	NM_001168378.1		c.1116G>A	p.Ser372Ser	synonymous	Exon 4 of 5	NP_001161850.1	Q8N9L1-3
	ZIC4	NM_001168379.2		c.1080G>A	p.Ser360Ser	synonymous	Exon 4 of 5	NP_001161851.1	Q8N9L1-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIC4	ENST00000383075.8	TSL:1 MANE Select	c.966G>A	p.Ser322Ser	synonymous	Exon 4 of 5	ENSP00000372553.3	Q8N9L1-1
	ZIC4	ENST00000525172.6	TSL:2	c.1116G>A	p.Ser372Ser	synonymous	Exon 4 of 5	ENSP00000435509.2	Q8N9L1-3
	ZIC4	ENST00000425731.7	TSL:2	c.1080G>A	p.Ser360Ser	synonymous	Exon 4 of 5	ENSP00000397695.3	Q8N9L1-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	8.3
DANN	Benign	0.96
PhyloP100		-0.69

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-147108756;