Genetic Variant ZKSCAN5:n.*2677G>T (chr7-99533211-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The ENST00000454175.1(ZKSCAN5):n.*2677G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 659,584 control chromosomes in the GnomAD database, including 467 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.

Frequency

Genomes: 𝑓 0.028 ( 115 hom., cov: 32)

Exomes 𝑓: 0.031 ( 352 hom. )

Consequence

ZKSCAN5
ENST00000454175.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.869

Publications

27 publications found

Variant links:

Genes affected

ZKSCAN5 (HGNC:12867): (zinc finger with KRAB and SCAN domains 5) This gene encodes a zinc finger protein of the Kruppel family. The protein contains a SCAN box and a KRAB A domain and may be involved in transcriptional regulation. A similar protein in mouse is differentially expressed in spermatogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ZKSCAN5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.03).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0278 (4239/152272) while in subpopulation NFE AF = 0.0355 (2413/68020). AF 95% confidence interval is 0.0343. There are 115 homozygotes in GnomAd4. There are 2210 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 115 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZKSCAN5	NM_145102.4 link	c.*962G>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000326775.10	NP_659570.1	Q9Y2L8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZKSCAN5	ENST00000454175.1 link	n.*2677G>T	non_coding_transcript_exon_variant	Exon 5 of 5	1		ENSP00000405716.1	F8WBD4
ZKSCAN5	ENST00000326775.10 link	c.*962G>T	3_prime_UTR_variant	Exon 7 of 7	1	NM_145102.4	ENSP00000322872.5	Q9Y2L8
ZKSCAN5	ENST00000394170.6 link	c.*962G>T	3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000377725.2	Q9Y2L8
ZKSCAN5	ENST00000454175.1 link	n.*2677G>T	3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000405716.1	F8WBD4

Frequencies

GnomAD3 genomes

AF:

0.0279

AC:

4240

AN:

152154

Hom.:

114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00673

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0241

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.0901

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0355

Gnomad OTH

AF:

0.0272

GnomAD2 exomes

AF:

0.0255

AC:

3318

AN:

130048

AF XY:

0.0252

show subpopulations

Gnomad AFR exome

AF:

0.00690

Gnomad AMR exome

AF:

0.0176

Gnomad ASJ exome

AF:

0.0234

Gnomad EAS exome

AF:

0.0000960

Gnomad FIN exome

AF:

0.0883

Gnomad NFE exome

AF:

0.0356

Gnomad OTH exome

AF:

0.0286

GnomAD4 exome

AF:

0.0314

AC:

15926

AN:

507312

Hom.:

352

Cov.:

AF XY:

0.0307

AC XY:

8485

AN XY:

276060

show subpopulations

African (AFR)

AF:

0.00644

AC:

AN:

14902

American (AMR)

AF:

0.0187

AC:

623

AN:

33316

Ashkenazi Jewish (ASJ)

AF:

0.0241

AC:

450

AN:

18668

East Asian (EAS)

AF:

0.0000707

AC:

AN:

28290

South Asian (SAS)

AF:

0.0144

AC:

885

AN:

61354

European-Finnish (FIN)

AF:

0.0865

AC:

2545

AN:

29408

Middle Eastern (MID)

AF:

0.0246

AC:

AN:

3854

European-Non Finnish (NFE)

AF:

0.0360

AC:

10415

AN:

289652

Other (OTH)

AF:

0.0292

AC:

815

AN:

27868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

527

1054

1580

2107

2634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.0278

AC:

4239

AN:

152272

Hom.:

115

Cov.:

AF XY:

0.0297

AC XY:

2210

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00671

AC:

279

AN:

41576

American (AMR)

AF:

0.0240

AC:

367

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0242

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.0141

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0901

AC:

956

AN:

10608

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0355

AC:

2413

AN:

68020

Other (OTH)

AF:

0.0270

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

204

408

611

815

1019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0334

Hom.:

177

Bravo

AF:

0.0223

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.8

(source)

DANN

Benign

0.70

PhyloP100

0.87

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over