Variant 3-40532915-C-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_198484.5(ZNF621):c.1145C>T(p.Pro382Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000563 in 1,420,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

ZNF621
NM_198484.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.146

Variant links:

Genes affected

ZNF621 (HGNC:24787): (zinc finger protein 621) 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 by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF621 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=0.1314019).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF621	NM_198484.5 linkuse as main transcript	c.1145C>T	p.Pro382Leu	missense_variant	5/5	ENST00000339296.10	NP_940886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF621	ENST00000339296.10 linkuse as main transcript	c.1145C>T	p.Pro382Leu	missense_variant	5/5	1	NM_198484.5	ENSP00000340841	P1	Q6ZSS3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

179862

Hom.:

AF XY:

0.0000105

AC XY:

AN XY:

95594

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000152

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000203

GnomAD4 exome

AF:

0.00000563

AC:

AN:

1420606

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

702816

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000213

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Jun 22, 2021

The c.1145C>T (p.P382L) alteration is located in exon 5 (coding exon 4) of the ZNF621 gene. This alteration results from a C to T substitution at nucleotide position 1145, causing the proline (P) at amino acid position 382 to be replaced by a leucine (L). 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

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.087

T;T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.84

.;T;T

M_CAP

Benign

0.0099

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;.

MutationTaster

Benign

0.99

D;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.073

Sift

Benign

0.14

T;T;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.68

P;P;P

Vest4

0.11

MutPred

0.51

Loss of disorder (P = 0.0326);Loss of disorder (P = 0.0326);.;

MVP

0.33

MPC

0.73

ClinPred

0.24

GERP RS

3.8

Varity_R

0.059

gMVP

0.12

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