chr18-35263988-A-G

Position:

• chr18-35263988-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001112734.4(ZSCAN30):​c.365T>C​(p.Met122Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00208 in 1,614,222 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (12 hom.)
• Consequence: ZSCAN30 NM_001112734.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029987395).
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSCAN30	NM_001112734.4	c.365T>C	p.Met122Thr	missense_variant	2/4	ENST00000333206.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSCAN30	ENST00000333206.10	c.365T>C	p.Met122Thr	missense_variant	2/4	1	NM_001112734.4	P1

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 211 AN: 152212 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00188

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00116 AC: 289 AN: 249880 Hom.: 2 AF XY: 0.00126 AC XY: 171 AN XY: 135724

Gnomad AFR exome AF: 0.000258

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00130

Gnomad NFE exome AF: 0.00169

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00216 AC: 3153 AN: 1461892 Hom.: 12 Cov.: 30 AF XY: 0.00201 AC XY: 1459 AN XY: 727248

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.00111

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000301

Gnomad4 FIN exome AF: 0.00120

Gnomad4 NFE exome AF: 0.00257

Gnomad4 OTH exome AF: 0.00136

GnomAD4 genome AF: 0.00139 AC: 212 AN: 152330 Hom.: 1 Cov.: 32 AF XY: 0.00137 AC XY: 102 AN XY: 74496

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.00188

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00194 Hom.: 0

Bravo AF: 0.00141

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000638 AC: 2

ESP6500EA AF: 0.00154 AC: 11

ExAC AF: 0.00101 AC: 122

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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 30, 2022

The c.365T>C (p.M122T) alteration is located in exon 3 (coding exon 1) of the ZSCAN30 gene. This alteration results from a T to C substitution at nucleotide position 365, causing the methionine (M) at amino acid position 122 to be replaced by a threonine (T). 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T;T;.;T;T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.030	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;.;.;.;.
MutationTaster	Benign	0.90	N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.3	N;N;.;.;.;.
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D;D;.;.;.;.
Sift4G	Uncertain	0.029	D;D;.;D;D;D
Polyphen		0.22	B;B;.;B;.;.
Vest4		0.26
MVP		0.40
MPC		0.047
ClinPred		0.058	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs199807098; hg19: chr18-32843952;