chr18-25225181-G-T

Position:

• chr18-25225181-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_015461.3(ZNF521):​c.2737C>A​(p.Pro913Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF521 NM_015461.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60

Genes affected

ZNF521 (HGNC:24605): (zinc finger protein 521) Enables protein domain specific binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within neuron fate commitment. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ZNF521

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF521	NM_015461.3	c.2737C>A	p.Pro913Thr	missense_variant	4/8	ENST00000361524.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF521	ENST00000361524.8	c.2737C>A	p.Pro913Thr	missense_variant	4/8	1	NM_015461.3	P1
ZNF521	ENST00000584787.5	c.2077C>A	p.Pro693Thr	missense_variant	3/7	1
ZNF521	ENST00000399425.6	c.2737C>A	p.Pro913Thr	missense_variant, NMD_transcript_variant	4/9	1
ZNF521	ENST00000538137.6	c.2737C>A	p.Pro913Thr	missense_variant	4/8	2		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	27
DANN	Benign	0.93
DEOGEN2	Benign	0.12	T;T;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.69	N;.;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.6	D;.;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.0050	D;.;.
Sift4G	Benign	0.34	T;T;T
Polyphen		1.0	D;.;D
Vest4		0.53
MutPred		0.81		Gain of MoRF binding (P = 0.0526);.;Gain of MoRF binding (P = 0.0526);
MVP		0.093
MPC		1.0
ClinPred		0.84	D
GERP RS		6.1
Varity_R		0.45
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-22805145;