Genetic Variant ZNF319:p.Gly422Ser (chr16-57997002-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020807.3(ZNF319):c.1264G>A(p.Gly422Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,601,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF319
NM_020807.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0640

Variant links:

Genes affected

ZNF319 (HGNC:13644): (zinc finger protein 319) Predicted to enable DNA-binding transcription activator 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 active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF319 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044399768).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF319	NM_020807.3 link	c.1264G>A	p.Gly422Ser	missense_variant	Exon 2 of 2	ENST00000299237.3	NP_065858.1	Q9P2F9
ZNF319	NM_001384365.1 link	c.1264G>A	p.Gly422Ser	missense_variant	Exon 2 of 2		NP_001371294.1
ZNF319	NM_001384366.1 link	c.1264G>A	p.Gly422Ser	missense_variant	Exon 3 of 3		NP_001371295.1
ZNF319	NM_001384367.1 link	c.1264G>A	p.Gly422Ser	missense_variant	Exon 3 of 3		NP_001371296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF319	ENST00000299237.3 link	c.1264G>A	p.Gly422Ser	missense_variant	Exon 2 of 2	1	NM_020807.3	ENSP00000299237.2		Q9P2F9

Frequencies

GnomAD3 genomes

AF:

0.00000675

AC:

AN:

148056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1453166

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722676

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000205

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000675

AC:

AN:

148056

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000294

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1264G>A (p.G422S) alteration is located in exon 2 (coding exon 1) of the ZNF319 gene. This alteration results from a G to A substitution at nucleotide position 1264, causing the glycine (G) at amino acid position 422 to be replaced by a serine (S). 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

0.097

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.1

DANN

Benign

0.83

DEOGEN2

Benign

0.020

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.64

M_CAP

Benign

0.0093

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.015

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.56

REVEL

Benign

0.017

Sift

Benign

0.55

Sift4G

Benign

0.73

Polyphen

0.15

Vest4

0.062

MutPred

0.49

Loss of catalytic residue at G422 (P = 0.011);

MVP

0.16

MPC

1.0

ClinPred

0.032

GERP RS

-0.96

Varity_R

0.031

gMVP

0.15

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