Variant 7-99512590-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_145102.4(ZKSCAN5):c.552T>C(p.Asn184Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,613,522 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 17 hom., cov: 31)

Exomes 𝑓: 0.0015 ( 21 hom. )

Consequence

ZKSCAN5
NM_145102.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0004359

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.233

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 7-99512590-T-C is Benign according to our data. Variant chr7-99512590-T-C is described in ClinVar as [Benign]. Clinvar id is 780699.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.233 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1632/152046) while in subpopulation AFR AF= 0.0368 (1528/41470). AF 95% confidence interval is 0.0353. There are 17 homozygotes in gnomad4. There are 781 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN5	NM_145102.4 linkuse as main transcript	c.552T>C	p.Asn184Asn	splice_region_variant, 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.552T>C	p.Asn184Asn	splice_region_variant, synonymous_variant	3/7	1	NM_145102.4	ENSP00000322872.5	Q9Y2L8
ZKSCAN5	ENST00000394170.6 linkuse as main transcript	c.552T>C	p.Asn184Asn	splice_region_variant, synonymous_variant	3/7	1		ENSP00000377725.2	Q9Y2L8
ZKSCAN5	ENST00000451158.5 linkuse as main transcript	c.552T>C	p.Asn184Asn	splice_region_variant, synonymous_variant	3/7	1		ENSP00000392104.1	Q9Y2L8
ZKSCAN5	ENST00000454175.1 linkuse as main transcript	n.552T>C		splice_region_variant, non_coding_transcript_exon_variant	2/5	1		ENSP00000405716.1	F8WBD4

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1629

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0369

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00327

AC:

817

AN:

250070

Hom.:

AF XY:

0.00252

AC XY:

341

AN XY:

135256

show subpopulations

Gnomad AFR exome

AF:

0.0383

Gnomad AMR exome

AF:

0.00189

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000700

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00155

AC:

2263

AN:

1461476

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1026

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.0390

Gnomad4 AMR exome

AF:

0.00211

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000530

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.0107

AC:

1632

AN:

152046

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

781

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0368

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00239

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.00131

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

9.5

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00044

dbscSNV1_RF

Benign

0.090

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

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