rs751843721

Variant names:

• chr13-99970359-G-A
• rs751843721
• NM_033132.5:c.1245C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-99970359-G-A
• chr13-99970359-G-C

Variant summary

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

The NM_033132.5(ZIC5):​c.1245C>T​(p.His415His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,386 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: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZIC5 NM_033132.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.45
• 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: 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=-0.44).
• BP7: Synonymous conserved (PhyloP=3.45 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC5	NM_033132.5	c.1245C>T	p.His415His	synonymous_variant	Exon 1 of 2	ENST00000267294.5	NP_149123.3
ZIC5	NR_146224.1	n.1551C>T		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZIC5	ENST00000267294.5	c.1245C>T	p.His415His	synonymous_variant	Exon 1 of 2	1	NM_033132.5	ENSP00000267294.4
ENSG00000297638	ENST00000749511.1	n.135+231G>A		intron_variant	Intron 1 of 1
ENSG00000297638	ENST00000749512.1	n.104+225G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455386 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724014

African (AFR) AF: 0.00 AC: 0 AN: 33180

American (AMR) AF: 0.00 AC: 0 AN: 44402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25922

East Asian (EAS) AF: 0.00 AC: 0 AN: 39276

South Asian (SAS) AF: 0.00 AC: 0 AN: 85970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109252

Other (OTH) AF: 0.00 AC: 0 AN: 60090

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		3.5

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: rs751843721; hg19: chr13-100622613;