Variant 19-7519443-C-G 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_018083.5(ZNF358):c.201C>G(p.Val67=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00659 in 1,614,144 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 39 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 68 hom. )

Consequence

ZNF358
NM_018083.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.176

Variant links:

Genes affected

ZNF358 (HGNC:16838): (zinc finger protein 358) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in several processes, including embryonic forelimb morphogenesis; neural tube development; and stem cell population maintenance. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF358 links:

LOC105372261 (HGNC:):

LOC105372261 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 19-7519443-C-G is Benign according to our data. Variant chr19-7519443-C-G is described in ClinVar as [Benign]. Clinvar id is 782557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.176 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (2084/152324) while in subpopulation AFR AF= 0.0369 (1534/41566). AF 95% confidence interval is 0.0354. There are 39 homozygotes in gnomad4. There are 975 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF358	NM_018083.5 linkuse as main transcript	c.201C>G	p.Val67=	synonymous_variant	2/2	ENST00000597229.2	NP_060553.4
LOC105372261	XR_936294.3 linkuse as main transcript	n.936+3399G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF358	ENST00000597229.2 linkuse as main transcript	c.201C>G	p.Val67=	synonymous_variant	2/2	2	NM_018083.5	ENSP00000472305	P1
ZNF358	ENST00000596712.1 linkuse as main transcript	c.201C>G	p.Val67=	synonymous_variant	2/2	3		ENSP00000472777

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2083

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0370

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00681

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00479

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.00657

AC:

1650

AN:

251104

Hom.:

AF XY:

0.00590

AC XY:

801

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.0356

Gnomad AMR exome

AF:

0.00451

Gnomad ASJ exome

AF:

0.0235

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000784

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00513

Gnomad OTH exome

AF:

0.00800

GnomAD4 exome

AF:

0.00585

AC:

8552

AN:

1461820

Hom.:

Cov.:

AF XY:

0.00564

AC XY:

4105

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0386

Gnomad4 AMR exome

AF:

0.00490

Gnomad4 ASJ exome

AF:

0.0232

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000742

Gnomad4 FIN exome

AF:

0.00137

Gnomad4 NFE exome

AF:

0.00512

Gnomad4 OTH exome

AF:

0.00743

GnomAD4 genome

AF:

0.0137

AC:

2084

AN:

152324

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

975

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0369

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00479

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00997

Hom.:

Bravo

AF:

0.0158

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00747

EpiControl

AF:

0.00652

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	May 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

1.3

DANN

Benign

0.86

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

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