7-100773851-A-G

Variant names:

• chr7-100773851-A-G
• rs78193191
• NM_003386.3:c.5765A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003386.3(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 NM_003386.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59
• Publications: 15 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003386.3. 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
	ZAN	NM_003386.3	MANE Select	c.5765A>G	p.His1922Arg	missense	Exon 31 of 48	NP_003377.2	Q9Y493-1
	ZAN	NM_173059.3		c.5765A>G	p.His1922Arg	missense	Exon 31 of 46	NP_775082.2	Q9Y493-6
	ZAN	NR_111917.2		n.5961A>G		non_coding_transcript_exon	Exon 31 of 48

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZAN	ENST00000613979.5	TSL:1 MANE Select	c.5765A>G	p.His1922Arg	missense	Exon 31 of 48	ENSP00000480750.1	Q9Y493-1
	ZAN	ENST00000620596.4	TSL:1	c.5765A>G	p.His1922Arg	missense	Exon 31 of 46	ENSP00000481742.1	Q9Y493-6
	ZAN	ENST00000538115.5	TSL:1	n.5765A>G		non_coding_transcript_exon	Exon 31 of 47	ENSP00000445091.2	Q9Y493-4

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

African (AFR) AF: 0.688 AC: 20448 AN: 29736

American (AMR) AF: 0.230 AC: 6691 AN: 29120

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 4418 AN: 12918

East Asian (EAS) AF: 0.166 AC: 6337 AN: 38072

South Asian (SAS) AF: 0.418 AC: 20222 AN: 48390

European-Finnish (FIN) AF: 0.292 AC: 6641 AN: 22712

Middle Eastern (MID) AF: 0.464 AC: 1118 AN: 2410

European-Non Finnish (NFE) AF: 0.345 AC: 145089 AN: 420712

Other (OTH) AF: 0.366 AC: 10578 AN: 28916

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

African (AFR) AF: 0.672 AC: 24493 AN: 36432

American (AMR) AF: 0.304 AC: 2670 AN: 8776

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 562 AN: 1612

East Asian (EAS) AF: 0.171 AC: 828 AN: 4834

South Asian (SAS) AF: 0.409 AC: 1180 AN: 2886

European-Finnish (FIN) AF: 0.286 AC: 1297 AN: 4530

Middle Eastern (MID) AF: 0.449 AC: 44 AN: 98

European-Non Finnish (NFE) AF: 0.342 AC: 8751 AN: 25590

Other (OTH) AF: 0.441 AC: 505 AN: 1144

Alfa AF: 0.642 Hom.: 12959

Bravo AF: 0.637

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
CADD	Benign	12
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.0043	T
PhyloP100		2.6
Sift4G	Benign	1.0	T
Vest4		0.053
gMVP		0.72

Splicing

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

Other links and lift over

dbSNP: rs78193191;