7-100773851-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003386.3(ZAN):​c.5765A>T​(p.His1922Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 22)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2571935).

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>T	p.His1922Leu	missense	Exon 31 of 48	NP_003377.2	Q9Y493-1
	ZAN	NM_173059.3		c.5765A>T	p.His1922Leu	missense	Exon 31 of 46	NP_775082.2	Q9Y493-6
	ZAN	NR_111917.2		n.5961A>T		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>T	p.His1922Leu	missense	Exon 31 of 48	ENSP00000480750.1	Q9Y493-1
	ZAN	ENST00000620596.4	TSL:1	c.5765A>T	p.His1922Leu	missense	Exon 31 of 46	ENSP00000481742.1	Q9Y493-6
	ZAN	ENST00000538115.5	TSL:1	n.5765A>T		non_coding_transcript_exon	Exon 31 of 47	ENSP00000445091.2	Q9Y493-4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 633084 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 315958

African (AFR) AF: 0.00 AC: 0 AN: 29744

American (AMR) AF: 0.00 AC: 0 AN: 29138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12922

East Asian (EAS) AF: 0.00 AC: 0 AN: 38076

South Asian (SAS) AF: 0.00 AC: 0 AN: 48402

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2410

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 420762

Other (OTH) AF: 0.00 AC: 0 AN: 28916

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 12959

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
CADD	Benign	17
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.26	T
PhyloP100		2.6
Sift4G	Uncertain	0.0040	D
Vest4		0.20
gMVP		0.82

Splicing

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

Other links and lift over

dbSNP: rs78193191;