rs201633210

Variant names:

• chr7-100738528-T-A
• rs201633210
• NM_003386.3:c.681T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-100738528-T-A
• chr7-100738528-T-C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003386.3(ZAN):​c.681T>A​(p.Thr227Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000173 in 1,503,908 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (3 hom., cov: 25)
  • Exomes 𝑓: 0.00017 (39 hom.)
• Consequence: ZAN NM_003386.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.12
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 7-100738528-T-A is Benign according to our data. Variant chr7-100738528-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2657764.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.12 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.681T>A	p.Thr227Thr	synonymous	Exon 7 of 48	NP_003377.2	Q9Y493-1
	ZAN	NM_173059.3		c.681T>A	p.Thr227Thr	synonymous	Exon 7 of 46	NP_775082.2	Q9Y493-6
	ZAN	NR_111917.2		n.877T>A		non_coding_transcript_exon	Exon 7 of 48

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZAN	ENST00000613979.5	TSL:1 MANE Select	c.681T>A	p.Thr227Thr	synonymous	Exon 7 of 48	ENSP00000480750.1	Q9Y493-1
	ZAN	ENST00000620596.4	TSL:1	c.681T>A	p.Thr227Thr	synonymous	Exon 7 of 46	ENSP00000481742.1	Q9Y493-6
	ZAN	ENST00000538115.5	TSL:1	n.681T>A		non_coding_transcript_exon	Exon 7 of 47	ENSP00000445091.2	Q9Y493-4

Frequencies

GnomAD3 genomes AF: 0.000219 AC: 31 AN: 141500 Hom.: 3 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00753

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000633

Gnomad OTH AF: 0.00103

GnomAD2 exomes AF: 0.000282 AC: 59 AN: 209292 AF XY: 0.000301

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00505

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000144

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000168 AC: 229 AN: 1362408 Hom.: 39 Cov.: 30 AF XY: 0.000167 AC XY: 113 AN XY: 676332

African (AFR) AF: 0.00 AC: 0 AN: 32060

American (AMR) AF: 0.00 AC: 0 AN: 40354

Ashkenazi Jewish (ASJ) AF: 0.00554 AC: 137 AN: 24720

East Asian (EAS) AF: 0.00 AC: 0 AN: 38348

South Asian (SAS) AF: 0.00 AC: 0 AN: 81826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.0000464 AC: 48 AN: 1034354

Other (OTH) AF: 0.000779 AC: 44 AN: 56506

GnomAD4 genome AF: 0.000219 AC: 31 AN: 141500 Hom.: 3 Cov.: 25 AF XY: 0.000275 AC XY: 19 AN XY: 69024

African (AFR) AF: 0.00 AC: 0 AN: 38762

American (AMR) AF: 0.00 AC: 0 AN: 14244

Ashkenazi Jewish (ASJ) AF: 0.00753 AC: 25 AN: 3322

East Asian (EAS) AF: 0.00 AC: 0 AN: 4910

South Asian (SAS) AF: 0.00 AC: 0 AN: 4542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000633 AC: 4 AN: 63160

Other (OTH) AF: 0.00103 AC: 2 AN: 1944

Alfa AF: 0.000811 Hom.: 4

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.9
DANN	Benign	0.57
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201633210; hg19: chr7-100336151;