rs760269746

Variant names:

• chr13-99970411-G-A
• rs760269746
• NM_033132.5:c.1193C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-99970411-G-A
• chr13-99970411-G-C
• chr13-99970411-G-T

Variant summary

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

The NM_033132.5(ZIC5):​c.1193C>T​(p.Pro398Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000017 in 1,176,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. P398Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000088 (0 hom., cov: 28)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: ZIC5 NM_033132.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.739
• Publications: 0 publications found

Genes affected

ZIC5 (HGNC:20322): (Zic family member 5) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. The encoded protein may act as a transcriptional repressor. Studies in mouse and Xenopus support a role for this gene in neural crest development. Elevated expression of this gene has been observed in various human cancers and may contribute to cancer progression. This gene is closely linked to a related family member on chromosome 13. [provided by RefSeq, Mar 2017]

ENSG00000297638 (HGNC:):

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 (MetaRNN=0.14182562).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033132.5. 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
	ZIC5	NM_033132.5	MANE Select	c.1193C>T	p.Pro398Leu	missense	Exon 1 of 2	NP_149123.3	Q96T25
	ZIC5	NR_146224.1		n.1499C>T		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIC5	ENST00000267294.5	TSL:1 MANE Select	c.1193C>T	p.Pro398Leu	missense	Exon 1 of 2	ENSP00000267294.4	Q96T25
	ENSG00000297638	ENST00000749511.1		n.135+283G>A		intron	N/A
	ENSG00000297638	ENST00000749512.1		n.104+277G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000883 AC: 1 AN: 113250 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000173

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.40e-7 AC: 1 AN: 1063290 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 513492

African (AFR) AF: 0.00 AC: 0 AN: 20898

American (AMR) AF: 0.00 AC: 0 AN: 9142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14022

East Asian (EAS) AF: 0.00 AC: 0 AN: 21056

South Asian (SAS) AF: 0.00 AC: 0 AN: 32384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3470

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 900930

Other (OTH) AF: 0.00 AC: 0 AN: 39474

GnomAD4 genome AF: 0.00000883 AC: 1 AN: 113250 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 55322

African (AFR) AF: 0.00 AC: 0 AN: 22730

American (AMR) AF: 0.00 AC: 0 AN: 12200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3028

East Asian (EAS) AF: 0.00 AC: 0 AN: 4046

South Asian (SAS) AF: 0.00 AC: 0 AN: 3758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 188

European-Non Finnish (NFE) AF: 0.0000173 AC: 1 AN: 57928

Other (OTH) AF: 0.00 AC: 0 AN: 1588

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.61
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.74
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.033
Sift	Benign	0.16	T
Sift4G	Benign	0.14	T
Polyphen		0.17	B
Vest4		0.35
MutPred		0.38		Gain of catalytic residue at P423 (P = 0)
MVP		0.24
ClinPred		0.43	T
GERP RS		3.1
Varity_R		0.054
gMVP		0.26
Mutation Taster		=98/2	polymorphism

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: rs760269746; hg19: chr13-100622665;