Genetic Variant ZAN:p.Thr227Thr (chr7-100738528-T-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_003386.3(ZAN):c.681T>C(p.Thr227Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,362,408 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T227T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0000015 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

ZAN
NM_003386.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

0 publications found

Variant links:

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]

ZAN links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP7

Synonymous conserved (PhyloP=-1.12 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZAN	NM_003386.3	MANE Select	c.681T>C	p.Thr227Thr	synonymous	Exon 7 of 48	NP_003377.2	Q9Y493-1
ZAN	NM_173059.3		c.681T>C	p.Thr227Thr	synonymous	Exon 7 of 46	NP_775082.2	Q9Y493-6
ZAN	NR_111917.2		n.877T>C		non_coding_transcript_exon	Exon 7 of 48

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

141500

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000147

AC:

AN:

1362408

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

676332

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32060

American (AMR)

AF:

0.00

AC:

AN:

40354

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24720

East Asian (EAS)

AF:

0.00

AC:

AN:

38348

South Asian (SAS)

AF:

0.00

AC:

AN:

81826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5646

European-Non Finnish (NFE)

AF:

0.00000193

AC:

AN:

1034354

Other (OTH)

AF:

0.00

AC:

AN:

56506

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

141500

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69024

African (AFR)

AF:

0.00

AC:

AN:

38762

American (AMR)

AF:

0.00

AC:

AN:

14244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3322

East Asian (EAS)

AF:

0.00

AC:

AN:

4910

South Asian (SAS)

AF:

0.00

AC:

AN:

4542

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9476

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

63160

Other (OTH)

AF:

0.00

AC:

AN:

1944

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.5

(source)

DANN

Benign

0.57

PhyloP100

-1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over