NM_145011.4:c.1359T>A

Variant names:

• chr10-37952139-A-T
• NM_145011.4:c.1359T>A
• ZNF25 p.Asn453Lys

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145011.4(ZNF25):​c.1359T>A​(p.Asn453Lys) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF25 NM_145011.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 0 publications found

Genes affected

ZNF25 (HGNC:13043): (zinc finger protein 25) 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044712126).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145011.4. 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
	ZNF25	NM_145011.4	MANE Select	c.1359T>A	p.Asn453Lys	missense	Exon 6 of 6	NP_659448.1	P17030-1
	ZNF25	NM_001329647.2		c.1371T>A	p.Asn457Lys	missense	Exon 7 of 7	NP_001316576.1
	ZNF25	NM_001329648.2		c.1371T>A	p.Asn457Lys	missense	Exon 8 of 8	NP_001316577.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF25	ENST00000302609.8	TSL:1 MANE Select	c.1359T>A	p.Asn453Lys	missense	Exon 6 of 6	ENSP00000302222.7	P17030-1
	ZNF25	ENST00000374633.5	TSL:1	n.1589T>A		non_coding_transcript_exon	Exon 7 of 7
	ZNF25	ENST00000897644.1		c.1392T>A	p.Asn464Lys	missense	Exon 6 of 6	ENSP00000567703.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.20
DANN	Benign	0.49
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.18	N
PhyloP100		-0.14
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.050
Sift	Benign	0.15	T
Sift4G	Uncertain	0.044	D
Varity_R		0.043
gMVP		0.018
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-38241067;