rs193921069

Positions:

• chr15-84621450-C-A

Variant summary

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

The NM_181877.4(ZSCAN2):​c.1255C>A​(p.Gln419Lys) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ZSCAN2 NM_181877.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.362

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)

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=0.048700005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSCAN2	NM_181877.4	c.1255C>A	p.Gln419Lys	missense_variant	3/3	ENST00000546148.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSCAN2	ENST00000546148.6	c.1255C>A	p.Gln419Lys	missense_variant	3/3	2	NM_181877.4	P1
ZSCAN2-AS1	ENST00000618330.3	n.1445+9849G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151058 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151176 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73834

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.026	T;T;T;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.014	N
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.049	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.83	N;N;.;.
MutationTaster	Benign	1.0	D;D;D;N;N;N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.50	N;N;N;N
REVEL	Benign	0.072
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.59	T;T;T;T
Polyphen		0.025	B;B;.;.
Vest4		0.11
MutPred		0.34		Gain of methylation at Q419 (P = 0);Gain of methylation at Q419 (P = 0);.;.;
MVP		0.14
MPC		0.49
ClinPred		0.57	D
GERP RS		4.8
Varity_R		0.15
gMVP		0.095

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: rs193921069; hg19: chr15-85164681; COSMIC: COSV57572585; COSMIC: COSV57572585;