rs1268766088

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-44567986-C-G
• chr3-44567986-C-T

Variant summary

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

The NM_001288590.2(ZKSCAN7):​c.667C>G​(p.Arg223Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000483 in 1,449,320 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R223W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: ZKSCAN7 NM_001288590.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

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

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>G	p.Arg223Gly	missense	Exon 4 of 6	NP_001275519.1	Q9P0L1-1
	ZKSCAN7	NM_018651.4		c.667C>G	p.Arg223Gly	missense	Exon 4 of 6	NP_061121.2
	ZKSCAN7	NM_001288592.2		c.217C>G	p.Arg73Gly	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>G	p.Arg223Gly	missense	Exon 4 of 6	ENSP00000395524.1	Q9P0L1-1
	ZKSCAN7	ENST00000273320.7	TSL:1	c.667C>G	p.Arg223Gly	missense	Exon 4 of 6	ENSP00000273320.3	Q9P0L1-1
	ZKSCAN7	ENST00000447279.2	TSL:1	c.217C>G	p.Arg73Gly	missense	Exon 3 of 6	ENSP00000405034.1	C9J6L6

Frequencies

GnomAD3 genomes AF: 0.00000667 AC: 1 AN: 149884 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000217

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000151 AC: 2 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000462 AC: 6 AN: 1299436 Hom.: 0 Cov.: 20 AF XY: 0.00000312 AC XY: 2 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: 0.0000804 AC: 6 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: 0.00 AC: 0 AN: 996540

Other (OTH) AF: 0.00 AC: 0 AN: 54314

GnomAD4 genome AF: 0.00000667 AC: 1 AN: 149884 Hom.: 0 Cov.: 27 AF XY: 0.0000137 AC XY: 1 AN XY: 72966

African (AFR) AF: 0.00 AC: 0 AN: 40518

American (AMR) AF: 0.00 AC: 0 AN: 14976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.000217 AC: 1 AN: 4608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67608

Other (OTH) AF: 0.00 AC: 0 AN: 2028

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.028	N
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.66
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.060
Sift	Benign	0.45	T
Sift4G	Benign	0.38	T
Polyphen		0.049	B
Vest4		0.072
MutPred		0.35		Loss of solvent accessibility (P = 0.0023)
MVP		0.17
MPC		0.083
ClinPred		0.071	T
GERP RS		0.62
Varity_R		0.056
gMVP		0.066
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.31		Position offset: 17

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1268766088; hg19: chr3-44609478;