6-28276500-G-A

Variant names:

• chr6-28276500-G-A
• NM_001023560.4:c.844G>A

Variant summary

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

The NM_001023560.4(ZSCAN26):​c.844G>A​(p.Gly282Ser) 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: ZSCAN26 NM_001023560.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.539

Genes affected

ZSCAN26 (HGNC:12978): (zinc finger and SCAN domain containing 26) 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. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000276302 (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=0.050679564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN26	NM_001023560.4	c.844G>A	p.Gly282Ser	missense_variant	Exon 4 of 4	ENST00000421553.7	NP_001018854.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN26	ENST00000421553.7	c.844G>A	p.Gly282Ser	missense_variant	Exon 4 of 4	1	NM_001023560.4	ENSP00000481707.1
ENSG00000276302	ENST00000621053.1	c.133+3713G>A		intron_variant	Intron 3 of 3	4		ENSP00000481142.1

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

May 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.844G>A (p.G282S) alteration is located in exon 4 (coding exon 3) of the ZSCAN26 gene. This alteration results from a G to A substitution at nucleotide position 844, causing the glycine (G) at amino acid position 282 to be replaced by a serine (S). 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	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	11
DANN	Benign	0.77
DEOGEN2	Benign	0.0045	T;.;.;T;.;T
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.62	T;.;T;T;T;.
MetaRNN	Benign	0.051	T;T;T;T;T;T
PrimateAI	Benign	0.31	T
Sift4G	Benign	0.64	T;D;D;T;D;T
Polyphen		0.090	.;.;.;B;.;.
Vest4		0.12
MVP		0.15
GERP RS		2.1
Varity_R		0.062
gMVP		0.076

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: chr6-28244277;