rs2293766

Variant names:

• chr7-100773735-G-A
• rs2293766
• NM_003386.3:c.5649G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-100773735-G-A
• chr7-100773735-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000613979.5(ZAN):​c.5649G>A​(p.Trp1883*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0428 in 1,609,900 control chromosomes in the GnomAD database, including 11,702 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.057 (1284 hom., cov: 33)
  • Exomes 𝑓: 0.041 (10418 hom.)
• Consequence: ZAN ENST00000613979.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.90
• Publications: 22 publications found

Genes affected

ZAN (HGNC:12857): (zonadhesin) This gene encodes a protein that functions in the species specificity of sperm adhesion to the egg zona pellucida. The encoded protein is located in the acrosome and may be involved in signaling or gamete recognition. An allelic polymorphism in this gene results in both functional and frameshifted alleles; the reference genome represents the functional allele. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2015]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000613979.5. 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
	ZAN	NM_003386.3	MANE Select	c.5649G>A	p.Trp1883*	stop_gained	Exon 31 of 48	NP_003377.2
	ZAN	NM_173059.3		c.5649G>A	p.Trp1883*	stop_gained	Exon 31 of 46	NP_775082.2
	ZAN	NR_111917.2		n.5845G>A		non_coding_transcript_exon	Exon 31 of 48

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZAN	ENST00000613979.5	TSL:1 MANE Select	c.5649G>A	p.Trp1883*	stop_gained	Exon 31 of 48	ENSP00000480750.1
	ZAN	ENST00000620596.4	TSL:1	c.5649G>A	p.Trp1883*	stop_gained	Exon 31 of 46	ENSP00000481742.1
	ZAN	ENST00000538115.5	TSL:1	n.5649G>A		non_coding_transcript_exon	Exon 31 of 47	ENSP00000445091.2

Frequencies

GnomAD3 genomes AF: 0.0568 AC: 8640 AN: 152088 Hom.: 1276 Cov.: 33

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.00529

Gnomad OTH AF: 0.0636

GnomAD2 exomes AF: 0.114 AC: 27608 AN: 241580 AF XY: 0.103

Gnomad AFR exome AF: 0.0210

Gnomad AMR exome AF: 0.346

Gnomad ASJ exome AF: 0.0455

Gnomad EAS exome AF: 0.530

Gnomad FIN exome AF: 0.0390

Gnomad NFE exome AF: 0.00622

Gnomad OTH exome AF: 0.0732

GnomAD4 exome AF: 0.0413 AC: 60195 AN: 1457690 Hom.: 10418 Cov.: 34 AF XY: 0.0424 AC XY: 30759 AN XY: 724778

African (AFR) AF: 0.0191 AC: 639 AN: 33372

American (AMR) AF: 0.332 AC: 14586 AN: 43986

Ashkenazi Jewish (ASJ) AF: 0.0446 AC: 1158 AN: 25988

East Asian (EAS) AF: 0.566 AC: 22367 AN: 39540

South Asian (SAS) AF: 0.128 AC: 10970 AN: 85430

European-Finnish (FIN) AF: 0.0359 AC: 1908 AN: 53096

Middle Eastern (MID) AF: 0.0201 AC: 116 AN: 5764

European-Non Finnish (NFE) AF: 0.00439 AC: 4874 AN: 1110246

Other (OTH) AF: 0.0594 AC: 3577 AN: 60268

GnomAD4 genome AF: 0.0569 AC: 8665 AN: 152210 Hom.: 1284 Cov.: 33 AF XY: 0.0659 AC XY: 4902 AN XY: 74426

African (AFR) AF: 0.0219 AC: 910 AN: 41562

American (AMR) AF: 0.218 AC: 3332 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3466

East Asian (EAS) AF: 0.512 AC: 2640 AN: 5154

South Asian (SAS) AF: 0.148 AC: 716 AN: 4822

European-Finnish (FIN) AF: 0.0388 AC: 412 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00529 AC: 360 AN: 68012

Other (OTH) AF: 0.0686 AC: 145 AN: 2114

Alfa AF: 0.0345 Hom.: 3877

Bravo AF: 0.0695

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00752 AC: 29

ESP6500AA AF: 0.0236 AC: 99

ESP6500EA AF: 0.00711 AC: 60

ExAC AF: 0.100 AC: 12110

Asia WGS AF: 0.283 AC: 983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	44
DANN	Uncertain	0.99
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.91	D
PhyloP100		4.9
Vest4		0.79
GERP RS		4.4
Mutation Taster		=34/166	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2293766; hg19: chr7-100371358; COSMIC: COSV61807659;