Variant 19-51945091-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001031721.4(ZNF613):c.1208A>G(p.Asn403Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF613
NM_001031721.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.52

Variant links:

Genes affected

ZNF613 (HGNC:25827): (zinc finger protein 613) 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 regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF613 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018789291).

BP6

Variant 19-51945091-A-G is Benign according to our data. Variant chr19-51945091-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2238248.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF613	NM_001031721.4 linkuse as main transcript	c.1208A>G	p.Asn403Ser	missense_variant	6/6	ENST00000293471.11	NP_001026891.2	Q6PF04-1
ZNF613	NM_024840.4 linkuse as main transcript	c.1100A>G	p.Asn367Ser	missense_variant	6/6		NP_079116.2	Q6PF04-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF613	ENST00000293471.11 linkuse as main transcript	c.1208A>G	p.Asn403Ser	missense_variant	6/6	1	NM_001031721.4	ENSP00000293471.5	Q6PF04-1
ZNF613	ENST00000391794.8 linkuse as main transcript	c.1100A>G	p.Asn367Ser	missense_variant	6/6	2		ENSP00000375671.3	Q6PF04-2
ZNF613	ENST00000601794.1 linkuse as main transcript	c.206A>G	p.Asn69Ser	missense_variant	1/2	2		ENSP00000490115.1	A0A1B0GUH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.30

DANN

Benign

0.53

DEOGEN2

Benign

0.0015

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00047

LIST_S2

Benign

0.36

T;T

M_CAP

Benign

0.00078

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.58

N;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.67

N;N

REVEL

Benign

0.018

Sift

Benign

1.0

T;T

Sift4G

Benign

0.83

T;T

Polyphen

0.0030

B;.

Vest4

0.031

MutPred

0.31

Loss of ubiquitination at K407 (P = 0.0736);.;

MVP

0.15

MPC

0.069

ClinPred

0.062

GERP RS

-2.8

Varity_R

0.038

gMVP

0.011

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over