Genetic Variant ZNF414:p.Gly382Val (chr19-8510719-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001146175.2(ZNF414):c.1145G>T(p.Gly382Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,397,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

ZNF414
NM_001146175.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.444

Publications

0 publications found

Variant links:

Genes affected

ZNF414 (HGNC:20630): (zinc finger protein 414) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ZNF414 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.096227586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF414	NM_001146175.2 link	c.1145G>T	p.Gly382Val	missense_variant	Exon 8 of 8	ENST00000393927.9	NP_001139647.1	Q96IQ9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF414	ENST00000393927.9 link	c.1145G>T	p.Gly382Val	missense_variant	Exon 8 of 8	1	NM_001146175.2	ENSP00000377504.3		Q96IQ9-2
ZNF414	ENST00000596772.5 link	c.*79G>T		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000471378.1		M0R0Q5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000358

AC:

AN:

1397356

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

689230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31528

American (AMR)

AF:

0.00

AC:

AN:

35542

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25120

East Asian (EAS)

AF:

0.00

AC:

AN:

35598

South Asian (SAS)

AF:

0.00

AC:

AN:

79000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.00000464

AC:

AN:

1077868

Other (OTH)

AF:

0.00

AC:

AN:

57902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Oct 04, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1145G>T (p.G382V) alteration is located in exon 8 (coding exon 8) of the ZNF414 gene. This alteration results from a G to T substitution at nucleotide position 1145, causing the glycine (G) at amino acid position 382 to be replaced by a valine (V). 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

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.58

M_CAP

Benign

0.054

MetaRNN

Benign

0.096

MetaSVM

Benign

-1.0

PhyloP100

0.44

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.3

REVEL

Benign

0.099

Sift

Benign

0.044

Sift4G

Benign

0.16

Vest4

0.40

MutPred

0.081

Loss of catalytic residue at G382 (P = 0.3559);

MVP

0.16

MPC

0.96

ClinPred

0.83

GERP RS

0.86

gMVP

0.29

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr19-8510719-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over