chr7-100023665-G-C

Position:

• chr7-100023665-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000324306.11(ZKSCAN1):​c.159G>C​(p.Glu53Asp) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZKSCAN1 ENST00000324306.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.14

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN1	NM_003439.4	c.159G>C	p.Glu53Asp	missense_variant	2/6	ENST00000324306.11	NP_003430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZKSCAN1	ENST00000324306.11	c.159G>C	p.Glu53Asp	missense_variant	2/6	1	NM_003439.4	ENSP00000323148	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Jul 07, 2022

The c.159G>C (p.E53D) alteration is located in exon 2 (coding exon 1) of the ZKSCAN1 gene. This alteration results from a G to C substitution at nucleotide position 159, causing the glutamic acid (E) at amino acid position 53 to be replaced by an aspartic acid (D). 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	0.23
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;T;.
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T;.;T;T
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.;.;.
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.5	N;N;D;.
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D;T;D;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.96	D;D;.;D
Vest4		0.64
MutPred		0.83		Gain of helix (P = 0.2059);.;Gain of helix (P = 0.2059);.;
MVP		0.35
MPC		1.3
ClinPred		0.94	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.48
gMVP		0.60

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: chr7-99621288;