3-44567986-C-T

Variant names:

• chr3-44567986-C-T
• rs1268766088
• NM_001288590.2:c.667C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001288590.2(ZKSCAN7):​c.667C>T​(p.Arg223Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000177 in 1,299,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: ZKSCAN7 NM_001288590.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.660
• Publications: 1 publications found

Genes affected

ZKSCAN7 (HGNC:12955): (zinc finger with KRAB and SCAN domains 7) 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 active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZKSCAN7-AS1 (HGNC:53964): (ZKSCAN7 ZNF cluster antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.101014555).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288590.2. 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
	ZKSCAN7	NM_001288590.2	MANE Select	c.667C>T	p.Arg223Trp	missense	Exon 4 of 6	NP_001275519.1	Q9P0L1-1
	ZKSCAN7	NM_018651.4		c.667C>T	p.Arg223Trp	missense	Exon 4 of 6	NP_061121.2
	ZKSCAN7	NM_001288592.2		c.217C>T	p.Arg73Trp	missense	Exon 3 of 6	NP_001275521.1	C9J6L6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZKSCAN7	ENST00000426540.6	TSL:2 MANE Select	c.667C>T	p.Arg223Trp	missense	Exon 4 of 6	ENSP00000395524.1	Q9P0L1-1
	ZKSCAN7	ENST00000273320.7	TSL:1	c.667C>T	p.Arg223Trp	missense	Exon 4 of 6	ENSP00000273320.3	Q9P0L1-1
	ZKSCAN7	ENST00000447279.2	TSL:1	c.217C>T	p.Arg73Trp	missense	Exon 3 of 6	ENSP00000405034.1	C9J6L6

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD2 exomes AF: 0.00000757 AC: 1 AN: 132122 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000197

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000177 AC: 23 AN: 1299436 Hom.: 0 Cov.: 20 AF XY: 0.0000156 AC XY: 10 AN XY: 641528

African (AFR) AF: 0.00 AC: 0 AN: 29398

American (AMR) AF: 0.00 AC: 0 AN: 33884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23102

East Asian (EAS) AF: 0.00 AC: 0 AN: 35078

South Asian (SAS) AF: 0.0000134 AC: 1 AN: 74590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4024

European-Non Finnish (NFE) AF: 0.0000201 AC: 20 AN: 996540

Other (OTH) AF: 0.0000368 AC: 2 AN: 54314

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.038	N
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.66
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.092
Sift	Benign	0.068	T
Sift4G	Benign	0.093	T
Polyphen		0.98	D
Vest4		0.17
MutPred		0.38		Loss of solvent accessibility (P = 0.0036)
MVP		0.31
MPC		0.25
ClinPred		0.64	D
GERP RS		0.62
Varity_R		0.052
gMVP		0.063
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs1268766088; hg19: chr3-44609478;