18-35245333-C-T

Variant names:

• chr18-35245333-C-T
• rs896822887
• NM_001135178.3:c.628C>T

Variant summary

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

The NM_001135178.3(ZNF397):​c.628C>T​(p.Pro210Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF397 NM_001135178.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.179
• Publications: 0 publications found

Genes affected

ZNF397 (HGNC:18818): (zinc finger protein 397) This gene encodes a protein with a N-terminal SCAN domain, and the longer isoform contains nine C2H2-type zinc finger repeats in the C-terminal domain. The protein localizes to centromeres during interphase and early prophase, and different isoforms can repress or activate transcription in transfection studies. Multiple transcript variants encoding different isoforms have been found for this gene. Additional variants have been described, but their biological validity has not been determined. [provided by RefSeq, Oct 2009]

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=0.035232753).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135178.3. 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
	ZNF397	NM_001135178.3	MANE Select	c.628C>T	p.Pro210Ser	missense	Exon 4 of 4	NP_001128650.1	Q8NF99-1
	ZNF397	NM_032347.3		c.628C>T	p.Pro210Ser	missense	Exon 4 of 6	NP_115723.1	Q8NF99-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF397	ENST00000330501.12	TSL:1 MANE Select	c.628C>T	p.Pro210Ser	missense	Exon 4 of 4	ENSP00000331577.6	Q8NF99-1
	ZNF397	ENST00000261333.10	TSL:1	c.628C>T	p.Pro210Ser	missense	Exon 4 of 6	ENSP00000261333.5	Q8NF99-2
	ZNF397	ENST00000589420.1	TSL:1	n.273C>T		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.4
DANN	Benign	0.91
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.53	N
PhyloP100		0.18
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.012
Sift	Benign	0.12	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.057
MutPred		0.31		Loss of catalytic residue at P210 (P = 0.0036)
MVP		0.048
MPC		0.15
ClinPred		0.033	T
GERP RS		0.29
Varity_R		0.038
gMVP		0.21
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs896822887; hg19: chr18-32825297;