rs78193191

Positions:

• chr7-100773851-A-G
• chr7-100773851-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000613979.5(ZAN):​c.5765A>G​(p.His1922Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 719,246 control chromosomes in the GnomAD database, including 30,217 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 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. H1922Y) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.47 (8643 hom., cov: 22)
  • Exomes 𝑓: 0.35 (21574 hom.)
• Consequence: ZAN ENST00000613979.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0042959154).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZAN	NM_003386.3	c.5765A>G	p.His1922Arg	missense_variant	31/48	ENST00000613979.5	NP_003377.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZAN	ENST00000613979.5	c.5765A>G	p.His1922Arg	missense_variant	31/48	1	NM_003386.3	ENSP00000480750	P1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 40382 AN: 86124 Hom.: 8614 Cov.: 22

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.441

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.441

GnomAD4 exome AF: 0.350 AC: 221542 AN: 632986 Hom.: 21574 Cov.: 0 AF XY: 0.351 AC XY: 110831 AN XY: 315894

Gnomad4 AFR exome AF: 0.688

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.342

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.418

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.345

Gnomad4 OTH exome AF: 0.366

GnomAD4 genome AF: 0.469 AC: 40464 AN: 86260 Hom.: 8643 Cov.: 22 AF XY: 0.463 AC XY: 19559 AN XY: 42256

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.441

Alfa AF: 0.642 Hom.: 12959

Bravo AF: 0.637

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
CADD	Benign	12
LIST_S2	Benign	0.17	.;.;T;T
MetaRNN	Benign	0.0043	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Vest4		0.053
gMVP		0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs78193191; hg19: -;