rs190931280

Variant names:

• chr3-147388874-T-C
• rs190931280
• NM_032153.6:c.1005-15A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-147388874-T-C
• chr3-147388874-T-G

Variant summary

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

The NM_032153.6(ZIC4):​c.1005-15A>G variant causes a intron change. The variant allele was found at a frequency of 0.00000478 in 627,532 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ZIC4 NM_032153.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.31
• 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]

ZIC4-AS1 (HGNC:40920): (ZIC4 antisense RNA 1)

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 (BayesDel_noAF=-0.31).

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.1005-15A>G		intron	N/A	NP_115529.2
	ZIC4	NM_001168378.1		c.1155-15A>G		intron	N/A	NP_001161850.1	Q8N9L1-3
	ZIC4	NM_001168379.2		c.1119-15A>G		intron	N/A	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.1005-15A>G		intron	N/A	ENSP00000372553.3	Q8N9L1-1
	ZIC4	ENST00000525172.6	TSL:2	c.1155-15A>G		intron	N/A	ENSP00000435509.2	Q8N9L1-3
	ZIC4	ENST00000425731.7	TSL:2	c.1119-15A>G		intron	N/A	ENSP00000397695.3	Q8N9L1-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248372 AF XY: 0.00000742

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000478 AC: 3 AN: 627532 Hom.: 0 Cov.: 0 AF XY: 0.00000585 AC XY: 2 AN XY: 341858

African (AFR) AF: 0.00 AC: 0 AN: 17630

American (AMR) AF: 0.0000231 AC: 1 AN: 43348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20966

East Asian (EAS) AF: 0.00 AC: 0 AN: 35980

South Asian (SAS) AF: 0.00 AC: 0 AN: 69462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 349822

Other (OTH) AF: 0.0000605 AC: 2 AN: 33056

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Benign	0.83
PhyloP100		4.3

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: rs190931280; hg19: chr3-147106661;