Variant 3-40482276-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145093.4(ZNF619):c.178+260G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF619
NM_001145093.4 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.103

Variant links:

Genes affected

ZNF619 (HGNC:26910): (zinc finger protein 619) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF619 links:

ZNF619 (HGNC:):

ZNF619 links:

ZNF620 (HGNC:28742): (zinc finger protein 620) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF620 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06903753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF619	NM_001145093.4 linkuse as main transcript	c.178+260G>T		intron_variant		ENST00000432264.4	NP_001138565.1	Q8N2I2-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF619	ENST00000432264.4 linkuse as main transcript	c.178+260G>T		intron_variant		5	NM_001145093.4	ENSP00000388710.2		Q8N2I2-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1399640

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690382

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:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.225G>T (p.K75N) alteration is located in exon 4 (coding exon 3) of the ZNF619 gene. This alteration results from a G to T substitution at nucleotide position 225, causing the lysine (K) at amino acid position 75 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.8

DANN

Uncertain

0.98

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.33

T;.

M_CAP

Benign

0.0062

MetaRNN

Benign

0.069

T;T

MetaSVM

Benign

-0.79

MutationTaster

Benign

1.0

D;D;D;D;D;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.055

Sift

Benign

0.46

T;T

Sift4G

Benign

0.27

T;T

Vest4

0.095

MutPred

0.40

Loss of ubiquitination at K75 (P = 0.0071);Loss of ubiquitination at K75 (P = 0.0071);

MVP

0.33

MPC

0.082

ClinPred

0.15

GERP RS

2.6

gMVP

0.049

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