18-35245676-T-G

Position:

• chr18-35245676-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135178.3(ZNF397):​c.971T>G​(p.Leu324Trp) 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. 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: -0.0660

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09408784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF397	NM_001135178.3	c.971T>G	p.Leu324Trp	missense_variant	4/4	ENST00000330501.12	NP_001128650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF397	ENST00000330501.12	c.971T>G	p.Leu324Trp	missense_variant	4/4	1	NM_001135178.3	ENSP00000331577	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.971T>G (p.L324W) alteration is located in exon 4 (coding exon 3) of the ZNF397 gene. This alteration results from a T to G substitution at nucleotide position 971, causing the leucine (L) at amino acid position 324 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.12
Sift	Benign	0.18	T
Sift4G	Benign	0.18	T
Polyphen		0.057	B
Vest4		0.35
MutPred		0.57		Gain of MoRF binding (P = 0.0231);
MVP		0.14
MPC		0.26
ClinPred		0.086	T
GERP RS		2.7
Varity_R		0.057
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr18-32825640;