NM_181877.4:c.254G>A

Variant names:

• chr15-84604181-G-A
• rs748156169
• NM_181877.4:c.254G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181877.4(ZSCAN2):​c.254G>A​(p.Arg85Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZSCAN2 NM_181877.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

Genes affected

ZSCAN2 (HGNC:20994): (zinc finger and SCAN domain containing 2) The protein encoded by this gene contains several copies of zinc finger motif, which is commonly found in transcriptional regulatory proteins. Studies in mice show that this gene is expressed during embryonic development, and specifically in the testis in adult mice, suggesting that it may play a role in regulating genes in germ cells. Alternative splicing of this gene results in several transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ZSCAN2-AS1 (HGNC:56673): (ZSCAN2 antisense RNA 1)

LOC105370947 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1693568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN2	NM_181877.4	c.254G>A	p.Arg85Gln	missense_variant	Exon 2 of 3	ENST00000546148.6	NP_870992.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN2	ENST00000546148.6	c.254G>A	p.Arg85Gln	missense_variant	Exon 2 of 3	2	NM_181877.4	ENSP00000445451.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461370 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726950

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.254G>A (p.R85Q) alteration is located in exon 2 (coding exon 1) of the ZSCAN2 gene. This alteration results from a G to A substitution at nucleotide position 254, causing the arginine (R) at amino acid position 85 to be replaced by a glutamine (Q). 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	0.078
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	.;T;T;.;.;.;T;.;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.030
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.88	D;.;.;T;T;T;T;T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.84	.;L;L;L;L;.;.;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.042
Sift	Benign	0.22	T;T;T;T;T;T;T;T;T
Sift4G	Uncertain	0.030	D;T;T;T;T;T;T;T;T
Polyphen		0.071, 0.59, 0.18, 0.64, 0.79, 0.75	.;B;B;P;B;.;P;P;P
Vest4		0.26, 0.24, 0.24, 0.27, 0.29, 0.29, 0.24
MutPred		0.57		Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);
MVP		0.21
MPC		0.090
ClinPred		0.62	D
GERP RS		3.4
Varity_R		0.067
gMVP		0.31

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: rs748156169; hg19: chr15-85147412;