18-35253550-A-T

Position:

• chr18-35253550-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001112734.4(ZSCAN30):​c.1385T>A​(p.Ile462Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN30 NM_001112734.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.561

Genes affected

ZSCAN30 (HGNC:33517): (zinc finger and SCAN domain containing 30) 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37098467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN30	NM_001112734.4	c.1385T>A	p.Ile462Asn	missense_variant	4/4	ENST00000333206.10	NP_001106205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN30	ENST00000333206.10	c.1385T>A	p.Ile462Asn	missense_variant	4/4	1	NM_001112734.4	ENSP00000329738	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Aug 11, 2022

The c.1385T>A (p.I462N) alteration is located in exon 5 (coding exon 3) of the ZSCAN30 gene. This alteration results from a T to A substitution at nucleotide position 1385, causing the isoleucine (I) at amino acid position 462 to be replaced by an asparagine (N). 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	0.94
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	.;T;T;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.046
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.12	T;.;T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.7	.;L;L;.
MutationTaster	Benign	1.0	D;D;D;N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.7	.;D;D;.
REVEL	Benign	0.098
Sift	Uncertain	0.0020	.;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;.
Polyphen		0.93	.;P;P;.
Vest4		0.45
MutPred		0.43		.;Loss of stability (P = 0.0102);Loss of stability (P = 0.0102);.;
MVP		0.54
MPC		0.30
ClinPred		0.97	D
GERP RS		2.0
Varity_R		0.58
gMVP		0.058

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: chr18-32833514;