19-36547639-C-G

Variant names:

• chr19-36547639-C-G
• rs778160715
• NM_020951.5:c.919G>C

Variant summary

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

The NM_020951.5(ZNF529):​c.919G>C​(p.Glu307Gln) 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. 13/21 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. E307K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF529 NM_020951.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.33
• Publications: 0 publications found

Genes affected

ZNF529 (HGNC:29328): (zinc finger protein 529) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.23424423).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020951.5. 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
	ZNF529	NM_020951.5	MANE Select	c.919G>C	p.Glu307Gln	missense	Exon 5 of 5	NP_066002.3	Q6P280
	ZNF529	NM_001145649.2		c.919G>C	p.Glu307Gln	missense	Exon 6 of 6	NP_001139121.1	Q6P280
	ZNF529	NM_001145650.2		c.865G>C	p.Glu289Gln	missense	Exon 5 of 5	NP_001139122.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF529	ENST00000591340.6	TSL:1 MANE Select	c.919G>C	p.Glu307Gln	missense	Exon 5 of 5	ENSP00000465578.1	Q6P280
	ZNF529	ENST00000867184.1		c.919G>C	p.Glu307Gln	missense	Exon 5 of 5	ENSP00000537243.1
	ZNF529	ENST00000867185.1		c.919G>C	p.Glu307Gln	missense	Exon 5 of 5	ENSP00000537244.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.00063	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.3
PrimateAI	Benign	0.36	T
REVEL	Benign	0.088
Sift4G	Uncertain	0.011	D
Vest4		0.071
MVP		0.52
MPC		0.36
ClinPred		0.84	D
GERP RS		3.3
PromoterAI		0.0076	Neutral
Varity_R		0.079
gMVP		0.030
Mutation Taster		=91/9	polymorphism

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: rs778160715; hg19: chr19-37038541;