NM_001012981.5:c.2633G>C

Variant names:

• chr16-25240087-C-G
• rs61742943
• NM_001012981.5:c.2633G>C

Variant summary

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

The NM_001012981.5(ZKSCAN2):​c.2633G>C​(p.Arg878Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R878Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZKSCAN2 NM_001012981.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 8 publications found

Genes affected

ZKSCAN2 (HGNC:25677): (zinc finger with KRAB and SCAN domains 2) 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

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=0.36890668).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012981.5. 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
	ZKSCAN2	NM_001012981.5	MANE Select	c.2633G>C	p.Arg878Pro	missense	Exon 7 of 7	NP_001012999.3	Q63HK3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZKSCAN2	ENST00000328086.12	TSL:1 MANE Select	c.2633G>C	p.Arg878Pro	missense	Exon 7 of 7	ENSP00000331626.7	Q63HK3-1
	ZKSCAN2	ENST00000919970.1		c.2141G>C	p.Arg714Pro	missense	Exon 6 of 6	ENSP00000590029.1
	ZKSCAN2	ENST00000964638.1		c.1457G>C	p.Arg486Pro	missense	Exon 5 of 5	ENSP00000634697.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.0090
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.13
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.027	D
Polyphen		0.91	P
Vest4		0.43
MutPred		0.66		Gain of methylation at R879 (P = 0.0676)
MVP		0.18
MPC		0.67
ClinPred		0.93	D
GERP RS		2.7
Varity_R		0.65
gMVP		0.65

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

dbSNP: rs61742943; hg19: chr16-25251408;