1-53216027-T-G

Variant names:

• chr1-53216027-T-G
• rs1134688
• NM_017887.3:c.369A>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_017887.3(CZIB):​c.369A>C​(p.Ser123Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,613,560 control chromosomes in the GnomAD database, including 33,329 homozygotes. 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: 𝑓 0.15 (2170 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31159 hom.)
• Consequence: CZIB NM_017887.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 19 publications found

Genes affected

CZIB (HGNC:26059): (CXXC motif containing zinc binding protein) Enables zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.078).
• BP7: Synonymous conserved (PhyloP=-2.52 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017887.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CZIB	NM_017887.3	MANE Select	c.369A>C	p.Ser123Ser	synonymous	Exon 7 of 8	NP_060357.1
	CZIB	NM_001304759.2		c.312A>C	p.Ser104Ser	synonymous	Exon 6 of 7	NP_001291688.1
	CZIB	NM_001304760.2		c.228A>C	p.Ser76Ser	synonymous	Exon 5 of 6	NP_001291689.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CZIB	ENST00000294360.5	TSL:1 MANE Select	c.369A>C	p.Ser123Ser	synonymous	Exon 7 of 8	ENSP00000294360.4
	CZIB	ENST00000470385.5	TSL:1	n.611A>C		non_coding_transcript_exon	Exon 6 of 7
	CZIB	ENST00000478839.1	TSL:2	n.1609A>C		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22981 AN: 152120 Hom.: 2169 Cov.: 32

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.0952

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.187

GnomAD2 exomes AF: 0.164 AC: 41184 AN: 251312 AF XY: 0.168

Gnomad AFR exome AF: 0.0459

Gnomad AMR exome AF: 0.128

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.0800

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.219

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.199 AC: 291264 AN: 1461322 Hom.: 31159 Cov.: 32 AF XY: 0.197 AC XY: 143536 AN XY: 726996

African (AFR) AF: 0.0438 AC: 1467 AN: 33474

American (AMR) AF: 0.130 AC: 5819 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 6669 AN: 26112

East Asian (EAS) AF: 0.0655 AC: 2600 AN: 39694

South Asian (SAS) AF: 0.103 AC: 8869 AN: 86224

European-Finnish (FIN) AF: 0.134 AC: 7126 AN: 53372

Middle Eastern (MID) AF: 0.172 AC: 991 AN: 5766

European-Non Finnish (NFE) AF: 0.221 AC: 245888 AN: 1111594

Other (OTH) AF: 0.196 AC: 11835 AN: 60368

GnomAD4 genome AF: 0.151 AC: 22998 AN: 152238 Hom.: 2170 Cov.: 32 AF XY: 0.144 AC XY: 10738 AN XY: 74430

African (AFR) AF: 0.0512 AC: 2130 AN: 41566

American (AMR) AF: 0.163 AC: 2495 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3468

East Asian (EAS) AF: 0.0776 AC: 402 AN: 5178

South Asian (SAS) AF: 0.0947 AC: 457 AN: 4828

European-Finnish (FIN) AF: 0.122 AC: 1297 AN: 10596

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14702 AN: 67994

Other (OTH) AF: 0.187 AC: 395 AN: 2110

Alfa AF: 0.177 Hom.: 2723

Bravo AF: 0.153

Asia WGS AF: 0.0710 AC: 250 AN: 3478

EpiCase AF: 0.227

EpiControl AF: 0.231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.82
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs1134688; hg19: chr1-53681699; COSMIC: COSV53758576; COSMIC: COSV53758576;