Genetic Variant NM_003386.3:c.681T>A (chr7-100738528-T-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

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

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:

AN:

141500

Hom.:

Cov.:

show subpopulations

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:

AN:

209292

AF XY:

0.000301

show subpopulations

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.:

Cov.:

AF XY:

0.000167

AC XY:

113

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:

0.00554

AC:

137

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:

0.0000464

AC:

AN:

1034354

Other (OTH)

AF:

0.000779

AC:

AN:

56506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000219

AC:

AN:

141500

Hom.:

Cov.:

AF XY:

0.000275

AC XY:

AN XY:

69024

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38762

American (AMR)

AF:

0.00

AC:

AN:

14244

Ashkenazi Jewish (ASJ)

AF:

0.00753

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:

0.0000633

AC:

AN:

63160

Other (OTH)

AF:

0.00103

AC:

AN:

1944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000811

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.9

(source)

DANN

Benign

0.57

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over