rs749584001

Variant names:

• chr16-57997002-C-G
• rs749584001
• NM_020807.3:c.1264G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-57997002-C-G
• chr16-57997002-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020807.3(ZNF319):​c.1264G>C​(p.Gly422Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. G422S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF319 NM_020807.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11677992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF319	NM_020807.3	c.1264G>C	p.Gly422Arg	missense_variant	Exon 2 of 2	ENST00000299237.3	NP_065858.1
ZNF319	NM_001384365.1	c.1264G>C	p.Gly422Arg	missense_variant	Exon 2 of 2		NP_001371294.1
ZNF319	NM_001384366.1	c.1264G>C	p.Gly422Arg	missense_variant	Exon 3 of 3		NP_001371295.1
ZNF319	NM_001384367.1	c.1264G>C	p.Gly422Arg	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.1264G>C	p.Gly422Arg	missense_variant	Exon 2 of 2	1	NM_020807.3	ENSP00000299237.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453174 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 722682

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.7
DANN	Benign	0.88
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.42	N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.56	N
REVEL	Benign	0.069
Sift	Benign	0.085	T
Sift4G	Benign	0.14	T
Polyphen		0.75	P
Vest4		0.29
MutPred		0.54		Gain of MoRF binding (P = 0.0341);
MVP		0.043
MPC		1.7
ClinPred		0.094	T
GERP RS		-0.96
Varity_R		0.035
gMVP		0.30

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: rs749584001; hg19: chr16-58030906;