6-28434469-C-T

Position:

• chr6-28434469-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001012455.2(ZSCAN23):​c.1166G>A​(p.Ser389Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,387,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: ZSCAN23 NM_001012455.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.336

Genes affected

ZSCAN23 (HGNC:21193): (zinc finger and SCAN domain containing 23) Enables sequence-specific double-stranded 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]

ZSCAN23 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048751563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN23	NM_001012455.2	c.1166G>A	p.Ser389Asn	missense_variant	4/4	ENST00000289788.5	NP_001012458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN23	ENST00000289788.5	c.1166G>A	p.Ser389Asn	missense_variant	4/4	1	NM_001012455.2	ENSP00000289788.4
ZSCAN23	ENST00000481983.5	n.*577G>A		non_coding_transcript_exon_variant	3/4	5		ENSP00000435430.1
ZSCAN23	ENST00000481983.5	n.*577G>A		3_prime_UTR_variant	3/4	5		ENSP00000435430.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1387452 Hom.: 0 Cov.: 31 AF XY: 0.00000293 AC XY: 2 AN XY: 682506

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000347

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

Jun 30, 2022

The c.1166G>A (p.S389N) alteration is located in exon 4 (coding exon 3) of the ZSCAN23 gene. This alteration results from a G to A substitution at nucleotide position 1166, causing the serine (S) at amino acid position 389 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	Benign	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.9
DANN	Benign	0.84
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.010
Sift	Benign	0.26	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.29		Loss of glycosylation at S389 (P = 0.0118);
MVP		0.081
MPC		0.24
ClinPred		0.052	T
GERP RS		0.23
Varity_R		0.042
gMVP		0.021

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: rs1761826221; hg19: chr6-28402246;