NM_024493.4:c.245A>G

Variant names:

• chr6-28359831-A-G
• NM_024493.4:c.245A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024493.4(ZKSCAN3):​c.245A>G​(p.Lys82Arg) 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: ZKSCAN3 NM_024493.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.630
• Publications: 0 publications found

Genes affected

ZKSCAN3 (HGNC:13853): (zinc finger with KRAB and SCAN domains 3) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and chromatin binding activity. Involved in several processes, including negative regulation of autophagy; negative regulation of cellular senescence; and regulation of transcription, DNA-templated. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4109617).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024493.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZKSCAN3	NM_024493.4	MANE Select	c.245A>G	p.Lys82Arg	missense	Exon 2 of 6	NP_077819.2	Q9BRR0-1
	ZKSCAN3	NM_001242894.2		c.245A>G	p.Lys82Arg	missense	Exon 3 of 7	NP_001229823.1	Q9BRR0-1
	ZKSCAN3	NM_001242895.2		c.-42-1493A>G		intron	N/A	NP_001229824.1	Q9BRR0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZKSCAN3	ENST00000252211.7	TSL:1 MANE Select	c.245A>G	p.Lys82Arg	missense	Exon 2 of 6	ENSP00000252211.2	Q9BRR0-1
	ZKSCAN3	ENST00000377255.3	TSL:1	c.245A>G	p.Lys82Arg	missense	Exon 3 of 7	ENSP00000366465.1	Q9BRR0-1
	ZKSCAN3	ENST00000881832.1		c.245A>G	p.Lys82Arg	missense	Exon 2 of 6	ENSP00000551891.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	4.0	H
PhyloP100		0.63
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.23
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.63		Loss of methylation at K82 (P = 0.0029)
MVP		0.49
MPC		1.9
ClinPred		0.97	D
GERP RS		3.7
Varity_R		0.20
gMVP		0.55
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

hg19: chr6-28327608;