16-57996546-C-T

Variant names:

• chr16-57996546-C-T
• rs1237605903
• NM_020807.3:c.1720G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_020807.3(ZNF319):​c.1720G>A​(p.Ala574Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000043 in 1,395,546 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: 35)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: ZNF319 NM_020807.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07035965).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF319	NM_020807.3	c.1720G>A	p.Ala574Thr	missense_variant	Exon 2 of 2	ENST00000299237.3	NP_065858.1
ZNF319	NM_001384365.1	c.1720G>A	p.Ala574Thr	missense_variant	Exon 2 of 2		NP_001371294.1
ZNF319	NM_001384366.1	c.1720G>A	p.Ala574Thr	missense_variant	Exon 3 of 3		NP_001371295.1
ZNF319	NM_001384367.1	c.1720G>A	p.Ala574Thr	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.1720G>A	p.Ala574Thr	missense_variant	Exon 2 of 2	1	NM_020807.3	ENSP00000299237.2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD3 exomes AF: 0.00000671 AC: 1 AN: 148990 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 82266

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000165

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000430 AC: 6 AN: 1395546 Hom.: 0 Cov.: 84 AF XY: 0.00000290 AC XY: 2 AN XY: 690160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000368

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 35

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1720G>A (p.A574T) 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 1720, causing the alanine (A) at amino acid position 574 to be replaced by a threonine (T). 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	0.086
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.86	L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.058
Sift	Benign	0.12	T
Sift4G	Benign	0.37	T
Polyphen		0.024	B
Vest4		0.11
MutPred		0.66		Gain of loop (P = 3e-04);
MVP		0.043
MPC		1.5
ClinPred		0.12	T
GERP RS		3.1
Varity_R		0.052
gMVP		0.24

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

Other links and lift over

dbSNP: rs1237605903; hg19: chr16-58030450;