Genetic Variant NM_003386.3:c.5769_5770insTT (chr7-100773854-G-GTT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_003386.3(ZAN):c.5769_5770insTT(p.Arg1924PhefsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,356,342 control chromosomes in the GnomAD database, including 175,140 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.51 ( 12117 hom., cov: 0)

Exomes 𝑓: 0.54 ( 163023 hom. )

Consequence

ZAN
NM_003386.3 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0220

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: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

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
ZAN	NM_003386.3	MANE Select	c.5769_5770insTT	p.Arg1924PhefsTer18	frameshift	Exon 31 of 48	NP_003377.2
ZAN	NM_173059.3		c.5769_5770insTT	p.Arg1924PhefsTer18	frameshift	Exon 31 of 46	NP_775082.2
ZAN	NR_111917.2		n.5965_5966insTT		non_coding_transcript_exon	Exon 31 of 48

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZAN	ENST00000613979.5	TSL:1 MANE Select	c.5769_5770insTT	p.Arg1924PhefsTer18	frameshift	Exon 31 of 48	ENSP00000480750.1
ZAN	ENST00000620596.4	TSL:1	c.5769_5770insTT	p.Arg1924PhefsTer18	frameshift	Exon 31 of 46	ENSP00000481742.1
ZAN	ENST00000538115.5	TSL:1	n.5769_5770insTT		non_coding_transcript_exon	Exon 31 of 47	ENSP00000445091.2

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

56132

AN:

110574

Hom.:

12123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.481

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.416

Gnomad ASJ

AF:

0.492

Gnomad EAS

AF:

0.0508

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.492

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.566

Gnomad OTH

AF:

0.532

GnomAD4 exome

AF:

0.538

AC:

669612

AN:

1245732

Hom.:

163023

Cov.:

AF XY:

0.537

AC XY:

332411

AN XY:

618616

show subpopulations

African (AFR)

AF:

0.484

AC:

5946

AN:

12282

American (AMR)

AF:

0.303

AC:

10513

AN:

34750

Ashkenazi Jewish (ASJ)

AF:

0.481

AC:

10242

AN:

21306

East Asian (EAS)

AF:

0.0320

AC:

902

AN:

28184

South Asian (SAS)

AF:

0.498

AC:

32015

AN:

64236

European-Finnish (FIN)

AF:

0.499

AC:

23028

AN:

46134

Middle Eastern (MID)

AF:

0.631

AC:

3149

AN:

4994

European-Non Finnish (NFE)

AF:

0.567

AC:

557972

AN:

983834

Other (OTH)

AF:

0.517

AC:

25845

AN:

50012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

21986

43972

65959

87945

109931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15714

31428

47142

62856

78570

<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:

0.507

AC:

56129

AN:

110610

Hom.:

12117

Cov.:

AF XY:

0.501

AC XY:

27141

AN XY:

54206

show subpopulations

African (AFR)

AF:

0.481

AC:

7778

AN:

16170

American (AMR)

AF:

0.415

AC:

5081

AN:

12256

Ashkenazi Jewish (ASJ)

AF:

0.492

AC:

1428

AN:

2900

East Asian (EAS)

AF:

0.0501

AC:

184

AN:

3676

South Asian (SAS)

AF:

0.457

AC:

1630

AN:

3566

European-Finnish (FIN)

AF:

0.492

AC:

4511

AN:

9174

Middle Eastern (MID)

AF:

0.687

AC:

184

AN:

268

European-Non Finnish (NFE)

AF:

0.566

AC:

34064

AN:

60228

Other (OTH)

AF:

0.530

AC:

845

AN:

1594

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1675

3350

5024

6699

8374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.022

Mutation Taster

=55/45

polymorphism

(source)

Splicing

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over