Variant rs11865038 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014699.4(ZNF646):c.*758C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,609,334 control chromosomes in the GnomAD database, including 141,029 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 16799 hom., cov: 33)

Exomes 𝑓: 0.40 ( 124230 hom. )

Consequence

ZNF646
NM_014699.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.71

Variant links:

Genes affected

ZNF646 (HGNC:29004): (zinc finger protein 646) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF646 links:

PRSS53 (HGNC:34407): (serine protease 53) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PRSS53 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF646	NM_014699.4 linkuse as main transcript	c.*758C>T		3_prime_UTR_variant	3/3	ENST00000300850.5
PRSS53	NM_001039503.3 linkuse as main transcript	c.1643-41G>A		intron_variant		ENST00000280606.7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF646	ENST00000300850.5 linkuse as main transcript	c.*758C>T	3_prime_UTR_variant	3/3	1	NM_014699.4	P2	O15015-2
PRSS53	ENST00000280606.7 linkuse as main transcript	c.1643-41G>A	intron_variant		1	NM_001039503.3	P1
ZNF646	ENST00000394979.2 linkuse as main transcript	c.*2036C>T	3_prime_UTR_variant	1/1			A2	O15015-1
PRSS53	ENST00000486499.1 linkuse as main transcript	n.5076G>A	non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68654

AN:

151922

Hom.:

16761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.716

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.404

GnomAD3 exomes

AF:

0.419

AC:

103847

AN:

247982

Hom.:

24527

AF XY:

0.430

AC XY:

57884

AN XY:

134708

show subpopulations

Gnomad AFR exome

AF:

0.623

Gnomad AMR exome

AF:

0.426

Gnomad ASJ exome

AF:

0.324

Gnomad EAS exome

AF:

0.103

Gnomad SAS exome

AF:

0.702

Gnomad FIN exome

AF:

0.384

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.401

GnomAD4 exome

AF:

0.399

AC:

581963

AN:

1457294

Hom.:

124230

Cov.:

AF XY:

0.406

AC XY:

294554

AN XY:

725046

show subpopulations

Gnomad4 AFR exome

AF:

0.624

Gnomad4 AMR exome

AF:

0.422

Gnomad4 ASJ exome

AF:

0.324

Gnomad4 EAS exome

AF:

0.0945

Gnomad4 SAS exome

AF:

0.694

Gnomad4 FIN exome

AF:

0.386

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.396

GnomAD4 genome

AF:

0.452

AC:

68745

AN:

152040

Hom.:

16799

Cov.:

AF XY:

0.454

AC XY:

33715

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.618

Gnomad4 AMR

AF:

0.423

Gnomad4 ASJ

AF:

0.301

Gnomad4 EAS

AF:

0.106

Gnomad4 SAS

AF:

0.715

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.388

Gnomad4 OTH

AF:

0.407

Alfa

AF:

0.383

Hom.:

12641

Bravo

AF:

0.451

Asia WGS

AF:

0.469

AC:

1627

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.90

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over