rs775064886

Variant names:

• chr3-147390947-C-A
• rs775064886
• NM_032153.6:c.988G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-147390947-C-A
• chr3-147390947-C-G
• chr3-147390947-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032153.6(ZIC4):​c.988G>T​(p.Ala330Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ZIC4 NM_032153.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054700017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC4	NM_032153.6	c.988G>T	p.Ala330Ser	missense_variant	Exon 4 of 5	ENST00000383075.8	NP_115529.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZIC4	ENST00000383075.8	c.988G>T	p.Ala330Ser	missense_variant	Exon 4 of 5	1	NM_032153.6	ENSP00000372553.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1457716 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 724950

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000833 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.91
DEOGEN2	Benign	0.039	T;.;.;T;T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.95
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.66	.;T;T;.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.055	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L;.;.;L;L;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.40	N;N;N;N;N;N
REVEL	Benign	0.040
Sift	Benign	0.50	T;T;T;T;T;T
Sift4G	Benign	0.77	T;T;T;T;T;T
Polyphen		0.0	B;.;.;B;B;.
Vest4		0.076
MutPred		0.23		Gain of phosphorylation at A330 (P = 0.0059);.;.;Gain of phosphorylation at A330 (P = 0.0059);Gain of phosphorylation at A330 (P = 0.0059);.;
MVP		0.32
MPC		0.46
ClinPred		0.10	T
GERP RS		3.1
Varity_R		0.044
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs775064886; hg19: chr3-147108734;