rs193920886

chr7-100033959-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003439.4(ZKSCAN1):c.1454G>A(p.Gly485Glu) variant causes a missense change. 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 (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZKSCAN1 NM_003439.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.66

Genes affected

ZKSCAN1 (HGNC:13101): (zinc finger with KRAB and SCAN domains 1) This gene encodes a member of the Kruppel C2H2-type zinc-finger family of proteins. This encoded protein may function as a transcription factor that regulates the expression of GABA type-A receptors in the brain. Transcripts from this gene have been shown to form stable and abundant circular RNAs. Elevated expression of this gene has been observed in gastric cancer and the encoded protein may stimulate migration and invasion of human gastric cancer cells. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30424404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZKSCAN1	NM_003439.4	c.1454G>A	p.Gly485Glu	missense_variant	6/6	ENST00000324306.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZKSCAN1	ENST00000324306.11	c.1454G>A	p.Gly485Glu	missense_variant	6/6	1	NM_003439.4	P1
ZKSCAN1	ENST00000426572.5	c.1346G>A	p.Gly449Glu	missense_variant	8/8	2
ZKSCAN1	ENST00000620510.1	c.1346G>A	p.Gly449Glu	missense_variant	6/6	5
ZKSCAN1	ENST00000535170.5	c.815G>A	p.Gly272Glu	missense_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;.;.
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.11	T;T;.;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-7.6	D;D;D;.
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.18
MutPred		0.53		.;Gain of solvent accessibility (P = 0.024);.;.;
MVP		0.41
MPC		1.6
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.80
gMVP		0.38

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: rs193920886; hg19: chr7-99631582;