chr16-57996917-T-G

Variant names:

• chr16-57996917-T-G
• rs745658522
• NM_020807.3:c.1349A>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_020807.3(ZNF319):​c.1349A>C​(p.His450Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H450R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ZNF319 NM_020807.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.68
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.975

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020807.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF319	NM_020807.3	MANE Select	c.1349A>C	p.His450Pro	missense	Exon 2 of 2	NP_065858.1	Q9P2F9
	ZNF319	NM_001384365.1		c.1349A>C	p.His450Pro	missense	Exon 2 of 2	NP_001371294.1	Q9P2F9
	ZNF319	NM_001384366.1		c.1349A>C	p.His450Pro	missense	Exon 3 of 3	NP_001371295.1	Q9P2F9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF319	ENST00000299237.3	TSL:1 MANE Select	c.1349A>C	p.His450Pro	missense	Exon 2 of 2	ENSP00000299237.2	Q9P2F9
	ZNF319	ENST00000858170.1		c.1349A>C	p.His450Pro	missense	Exon 2 of 2	ENSP00000528229.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.66	T
M_CAP	Pathogenic	0.73	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	0.81	D
MutationAssessor	Pathogenic	3.7	H
PhyloP100		5.7
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-9.4	D
REVEL	Pathogenic	0.91
Sift	Uncertain	0.012	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.78		Loss of helix (P = 0.0558)
MVP		0.92
MPC		2.6
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.87
gMVP		0.92

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

Other links and lift over

dbSNP: rs745658522; hg19: chr16-58030821;