Variant X-152919040-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001395254.1(ZNF185):c.489G>A(p.Glu163Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00551 in 1,208,629 control chromosomes in the GnomAD database, including 23 homozygotes. There are 2,102 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 3 hom., 232 hem., cov: 23)

Exomes 𝑓: 0.0053 ( 20 hom. 1870 hem. )

Consequence

ZNF185
NM_001395254.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0660

Variant links:

Genes affected

ZNF185 (HGNC:12976): (zinc finger protein 185 with LIM domain) Zinc-finger proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This gene encodes a LIM-domain zinc finger protein. The LIM domain is composed of two contiguous zinc finger domains, separated by a two-amino acid residue hydrophobic linker. The LIM domain mediates protein:protein interactions. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, May 2010]

ZNF185 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant X-152919040-G-A is Benign according to our data. Variant chrX-152919040-G-A is described in ClinVar as [Benign]. Clinvar id is 782829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.066 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00533 (5848/1096971) while in subpopulation MID AF= 0.0438 (181/4132). AF 95% confidence interval is 0.0386. There are 20 homozygotes in gnomad4_exome. There are 1870 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF185	NM_001395254.1 linkuse as main transcript	c.489G>A	p.Glu163Glu	synonymous_variant	8/25	ENST00000695776.1	NP_001382183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF185	ENST00000695776.1 linkuse as main transcript	c.489G>A	p.Glu163Glu	synonymous_variant	8/25		NM_001395254.1	ENSP00000512166.1		A0A8Q3WKR1

Frequencies

GnomAD3 genomes

AF:

0.00729

AC:

814

AN:

111605

Hom.:

Cov.:

AF XY:

0.00687

AC XY:

232

AN XY:

33779

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0206

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.00492

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00191

Gnomad FIN

AF:

0.000325

Gnomad MID

AF:

0.0417

Gnomad NFE

AF:

0.00577

Gnomad OTH

AF:

0.0180

GnomAD3 exomes

AF:

0.00513

AC:

908

AN:

176968

Hom.:

AF XY:

0.00490

AC XY:

319

AN XY:

65082

show subpopulations

Gnomad AFR exome

AF:

0.0118

Gnomad AMR exome

AF:

0.00555

Gnomad ASJ exome

AF:

0.00474

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00216

Gnomad FIN exome

AF:

0.000571

Gnomad NFE exome

AF:

0.00625

Gnomad OTH exome

AF:

0.00960

GnomAD4 exome

AF:

0.00533

AC:

5848

AN:

1096971

Hom.:

Cov.:

AF XY:

0.00516

AC XY:

1870

AN XY:

362523

show subpopulations

Gnomad4 AFR exome

AF:

0.0132

Gnomad4 AMR exome

AF:

0.00685

Gnomad4 ASJ exome

AF:

0.00449

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00197

Gnomad4 FIN exome

AF:

0.000718

Gnomad4 NFE exome

AF:

0.00534

Gnomad4 OTH exome

AF:

0.00788

GnomAD4 genome

AF:

0.00727

AC:

812

AN:

111658

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

232

AN XY:

33842

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.0118

Gnomad4 ASJ

AF:

0.00492

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00191

Gnomad4 FIN

AF:

0.000325

Gnomad4 NFE

AF:

0.00577

Gnomad4 OTH

AF:

0.0178

Alfa

AF:

0.00727

Hom.:

Bravo

AF:

0.00940

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 02, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.4

DANN

Benign

0.33

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

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