NM_003386.3:c.322G>C

Variant names:

• chr7-100736877-G-C
• rs377492790
• NM_003386.3:c.322G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003386.3(ZAN):​c.322G>C​(p.Asp108His) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 27)
• Consequence: ZAN NM_003386.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08891454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZAN	NM_003386.3	c.322G>C	p.Asp108His	missense_variant	Exon 5 of 48	ENST00000613979.5	NP_003377.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZAN	ENST00000613979.5	c.322G>C	p.Asp108His	missense_variant	Exon 5 of 48	1	NM_003386.3	ENSP00000480750.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.27
DANN	Benign	0.24
DEOGEN2	Benign	0.013	T;.;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.60	.;.;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.089	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.77	N;N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.2	.;.;.;N
REVEL	Benign	0.099
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.65	P;.;P;.
Vest4		0.27
MutPred		0.51		Loss of stability (P = 0.1834);Loss of stability (P = 0.1834);Loss of stability (P = 0.1834);Loss of stability (P = 0.1834);
MVP		0.055
MPC		0.44
ClinPred		0.22	T
GERP RS		-6.0
Varity_R		0.051
gMVP		0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs377492790; hg19: chr7-100334500;