6-28153709-C-G

Variant summary

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

The NM_006298.4(ZKSCAN8):c.1429C>G(p.Leu477Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZKSCAN8 NM_006298.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13

Genes affected

ZKSCAN8 (HGNC:12983): (zinc finger with KRAB and SCAN domains 8) 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. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZKSCAN8	NM_006298.4	c.1429C>G	p.Leu477Val	missense_variant	6/6	ENST00000330236.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZKSCAN8	ENST00000330236.7	c.1429C>G	p.Leu477Val	missense_variant	6/6	1	NM_006298.4	P1
ZKSCAN8	ENST00000457389.6	c.1429C>G	p.Leu477Val	missense_variant	7/7	1		P1
ZKSCAN8	ENST00000606198.5	c.*966C>G		3_prime_UTR_variant, NMD_transcript_variant	6/6	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 20, 2023

The c.1429C>G (p.L477V) alteration is located in exon 6 (coding exon 5) of the ZKSCAN8 gene. This alteration results from a C to G substitution at nucleotide position 1429, causing the leucine (L) at amino acid position 477 to be replaced by a valine (V). 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	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.10	T;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Benign	0.54	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	0.98	D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.7	D;D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.076	T;T
Polyphen		1.0	D;D
Vest4		0.32
MutPred		0.83		Gain of MoRF binding (P = 0.0881);Gain of MoRF binding (P = 0.0881);
MVP		0.55
MPC		1.0
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.69
gMVP		0.48

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: chr6-28121487;