6-28153727-A-G

Variant summary

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

The NM_006298.4(ZKSCAN8):c.1447A>G(p.Ser483Gly) 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. 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: 1.45

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28126162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZKSCAN8	NM_006298.4	c.1447A>G	p.Ser483Gly	missense_variant	6/6	ENST00000330236.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZKSCAN8	ENST00000330236.7	c.1447A>G	p.Ser483Gly	missense_variant	6/6	1	NM_006298.4	P1
ZKSCAN8	ENST00000457389.6	c.1447A>G	p.Ser483Gly	missense_variant	7/7	1		P1
ZKSCAN8	ENST00000606198.5	c.*984A>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

Dec 16, 2023

The c.1447A>G (p.S483G) alteration is located in exon 6 (coding exon 5) of the ZKSCAN8 gene. This alteration results from a A to G substitution at nucleotide position 1447, causing the serine (S) at amino acid position 483 to be replaced by a glycine (G). 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	Uncertain	0.34
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.012	T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.079	N
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	0.71	N;N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.99	D;D
Vest4		0.31
MutPred		0.53		Loss of stability (P = 0.0119);Loss of stability (P = 0.0119);
MVP		0.45
MPC		0.92
ClinPred		0.83	D
GERP RS		6.0
Varity_R		0.28
gMVP		0.12

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: chr6-28121505;