Variant 7-99512482-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_145102.4(ZKSCAN5):c.444G>A(p.Arg148Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,613,796 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 38 hom., cov: 31)

Exomes 𝑓: 0.0013 ( 30 hom. )

Consequence

ZKSCAN5
NM_145102.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.42

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 made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 7-99512482-G-A is Benign according to our data. Variant chr7-99512482-G-A is described in ClinVar as [Benign]. Clinvar id is 783500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.42 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1948/152276) while in subpopulation AFR AF= 0.0444 (1846/41542). AF 95% confidence interval is 0.0427. There are 38 homozygotes in gnomad4. There are 950 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN5	NM_145102.4 linkuse as main transcript	c.444G>A	p.Arg148Arg	synonymous_variant	3/7	ENST00000326775.10	NP_659570.1	Q9Y2L8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZKSCAN5	ENST00000326775.10 linkuse as main transcript	c.444G>A	p.Arg148Arg	synonymous_variant	3/7	1	NM_145102.4	ENSP00000322872.5	Q9Y2L8
ZKSCAN5	ENST00000394170.6 linkuse as main transcript	c.444G>A	p.Arg148Arg	synonymous_variant	3/7	1		ENSP00000377725.2	Q9Y2L8
ZKSCAN5	ENST00000451158.5 linkuse as main transcript	c.444G>A	p.Arg148Arg	synonymous_variant	3/7	1		ENSP00000392104.1	Q9Y2L8
ZKSCAN5	ENST00000454175.1 linkuse as main transcript	n.444G>A		non_coding_transcript_exon_variant	2/5	1		ENSP00000405716.1	F8WBD4

Frequencies

GnomAD3 genomes

AF:

0.0128

AC:

1948

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0446

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00344

AC:

864

AN:

250874

Hom.:

AF XY:

0.00240

AC XY:

326

AN XY:

135590

show subpopulations

Gnomad AFR exome

AF:

0.0465

Gnomad AMR exome

AF:

0.00264

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000655

GnomAD4 exome

AF:

0.00129

AC:

1881

AN:

1461520

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

801

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.0448

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000612

Gnomad4 OTH exome

AF:

0.00273

GnomAD4 genome

AF:

0.0128

AC:

1948

AN:

152276

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

950

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0444

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00544

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over