19-37380331-C-A

Variant names:

• chr19-37380331-C-A
• rs780232583
• NM_032453.2:c.215C>A

Variant summary

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

The NM_032453.2(ZNF527):​c.215C>A​(p.Pro72Gln) 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. 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. P72L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF527 NM_032453.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 1 publications found

Genes affected

ZNF527 (HGNC:29385): (zinc finger protein 527) Predicted to enable DNA-binding transcription factor 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: 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=0.263758).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032453.2. 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
	ZNF527	NM_032453.2	MANE Select	c.215C>A	p.Pro72Gln	missense	Exon 4 of 5	NP_115829.1	Q8NB42-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF527	ENST00000436120.7	TSL:4 MANE Select	c.215C>A	p.Pro72Gln	missense	Exon 4 of 5	ENSP00000390179.2	Q8NB42-1
	ZNF527	ENST00000483919.5	TSL:1	c.215C>A	p.Pro72Gln	missense	Exon 4 of 5	ENSP00000468344.1	Q0P6G1
	ZNF527	ENST00000969391.1		c.215C>A	p.Pro72Gln	missense	Exon 4 of 5	ENSP00000639450.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.7
PrimateAI	Benign	0.35	T
REVEL	Benign	0.16
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.46
MutPred		0.51		Gain of solvent accessibility (P = 0.1116)
MVP		0.58
MPC		0.69
ClinPred		0.91	D
GERP RS		4.5
Varity_R		0.43
gMVP		0.43
Mutation Taster		=86/14	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: rs780232583; hg19: chr19-37871233;