6-28434925-T-C

Position:

• chr6-28434925-T-C

Variant summary

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

The NM_001012455.2(ZSCAN23):​c.710A>G​(p.Glu237Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN23 NM_001012455.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

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=0.053131223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN23	NM_001012455.2	c.710A>G	p.Glu237Gly	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.710A>G	p.Glu237Gly	missense_variant	4/4	1	NM_001012455.2	ENSP00000289788.4
ZSCAN23	ENST00000481983.5	n.*121A>G		non_coding_transcript_exon_variant	3/4	5		ENSP00000435430.1
ZSCAN23	ENST00000486481.1	n.406A>G		non_coding_transcript_exon_variant	3/3	2
ZSCAN23	ENST00000481983.5	n.*121A>G		3_prime_UTR_variant	3/4	5		ENSP00000435430.1

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

Nov 24, 2024

The c.710A>G (p.E237G) alteration is located in exon 4 (coding exon 3) of the ZSCAN23 gene. This alteration results from a A to G substitution at nucleotide position 710, causing the glutamic acid (E) at amino acid position 237 to be replaced by a glycine (G). 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	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.020
Sift	Benign	0.11	T
Sift4G	Benign	0.16	T
Polyphen		0.0020	B
Vest4		0.11
MutPred		0.25		Loss of ubiquitination at K238 (P = 0.033);
MVP		0.22
MPC		0.31
ClinPred		0.059	T
GERP RS		2.1
Varity_R		0.14
gMVP		0.10

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: chr6-28402702;