16-57997216-C-T

Variant names:

• chr16-57997216-C-T
• NM_020807.3:c.1050G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020807.3(ZNF319):​c.1050G>A​(p.Met350Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ZNF319 NM_020807.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.89

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF319	NM_020807.3	c.1050G>A	p.Met350Ile	missense_variant	Exon 2 of 2	ENST00000299237.3	NP_065858.1
ZNF319	NM_001384365.1	c.1050G>A	p.Met350Ile	missense_variant	Exon 2 of 2		NP_001371294.1
ZNF319	NM_001384366.1	c.1050G>A	p.Met350Ile	missense_variant	Exon 3 of 3		NP_001371295.1
ZNF319	NM_001384367.1	c.1050G>A	p.Met350Ile	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	c.1050G>A	p.Met350Ile	missense_variant	Exon 2 of 2	1	NM_020807.3	ENSP00000299237.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1050G>A (p.M350I) 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 1050, causing the methionine (M) at amino acid position 350 to be replaced by an isoleucine (I). 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	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.75	N
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.043	D
Polyphen		0.99	D
Vest4		0.61
MutPred		0.55		Loss of MoRF binding (P = 0.0802);
MVP		0.18
MPC		2.2
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.52
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr16-58031120;