16-57997325-G-A

Variant names:

• chr16-57997325-G-A
• NM_020807.3:c.941C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020807.3(ZNF319):​c.941C>T​(p.Pro314Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 9.98

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.81

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF319	NM_020807.3	c.941C>T	p.Pro314Leu	missense_variant	Exon 2 of 2	ENST00000299237.3	NP_065858.1
ZNF319	NM_001384365.1	c.941C>T	p.Pro314Leu	missense_variant	Exon 2 of 2		NP_001371294.1
ZNF319	NM_001384366.1	c.941C>T	p.Pro314Leu	missense_variant	Exon 3 of 3		NP_001371295.1
ZNF319	NM_001384367.1	c.941C>T	p.Pro314Leu	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.941C>T	p.Pro314Leu	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

Oct 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.941C>T (p.P314L) alteration is located in exon 2 (coding exon 1) of the ZNF319 gene. This alteration results from a C to T substitution at nucleotide position 941, causing the proline (P) at amino acid position 314 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	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	2.9	M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-8.7	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.028	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.32		Loss of glycosylation at S310 (P = 0.09);
MVP		0.33
MPC		2.2
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.61
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-58031229;