16-71475585-C-A

Variant names:

• chr16-71475585-C-A
• rs145033718
• NM_006961.4:c.962G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006961.4(ZNF19):​c.962G>T​(p.Arg321Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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. R321H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF19 NM_006961.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 2 publications found

Genes affected

ZNF19 (HGNC:12981): (zinc finger protein 19) The protein encoded by this gene contains a zinc finger, a nucleic acid-binding domain present in many transcription factors. This gene is located in a region next to ZNF23, a gene also encoding a zinc finger protein, on chromosome 16. [provided by RefSeq, Jul 2008]

ENSG00000261611 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14513937).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006961.4. 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
	ZNF19	NM_006961.4	MANE Select	c.962G>T	p.Arg321Leu	missense	Exon 6 of 6	NP_008892.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF19	ENST00000288177.10	TSL:1 MANE Select	c.962G>T	p.Arg321Leu	missense	Exon 6 of 6	ENSP00000288177.5	P17023-1
	ENSG00000261611	ENST00000561908.1	TSL:2	n.274+2643G>T		intron	N/A	ENSP00000463741.1	J3QLW9
	ZNF19	ENST00000564230.5	TSL:2	c.962G>T	p.Arg321Leu	missense	Exon 6 of 6	ENSP00000458105.1	P17023-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.023	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.086
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.049
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.012	D
Polyphen		0.17	B
Vest4		0.26
MutPred		0.62		Loss of disorder (P = 0.0628)
MVP		0.22
MPC		0.045
ClinPred		0.98	D
GERP RS		0.49
Varity_R		0.44
gMVP		0.082

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: rs145033718; hg19: chr16-71509488;