13-99982147-C-T

Variant names:

• chr13-99982147-C-T
• NM_007129.5:c.83C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007129.5(ZIC2):​c.83C>T​(p.Ala28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000842 in 1,187,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A28G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: ZIC2 NM_007129.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05

Genes affected

ZIC2 (HGNC:12873): (Zic family member 2) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This protein functions as a transcriptional repressor and may regulate tissue specific expression of dopamine receptor D1. Expansion of an alanine repeat in the C-terminus of the encoded protein and other mutations in this gene cause holoprosencephaly type 5. Holoprosencephaly is the most common structural anomaly of the human brain. A polyhistidine tract polymorphism in this gene may be associated with increased risk of neural tube defects. This gene is closely linked to a gene encoding zinc finger protein of the cerebellum 5, a related family member on chromosome 13. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41056296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC2	NM_007129.5	c.83C>T	p.Ala28Val	missense_variant	Exon 1 of 3	ENST00000376335.8	NP_009060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZIC2	ENST00000376335.8	c.83C>T	p.Ala28Val	missense_variant	Exon 1 of 3	1	NM_007129.5	ENSP00000365514.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.42e-7 AC: 1 AN: 1187516 Hom.: 0 Cov.: 30 AF XY: 0.00000174 AC XY: 1 AN XY: 574968

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000102

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.059
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.11
Sift	Benign	0.15	T
Sift4G	Benign	0.21	T
Polyphen		1.0	D
Vest4		0.30
MutPred		0.41		Gain of catalytic residue at A28 (P = 0);
MVP		0.80
ClinPred		0.84	D
GERP RS		2.9
Varity_R		0.12
gMVP		0.39

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: chr13-100634401;