chr3-44565590-C-G

Variant names:

• chr3-44565590-C-G
• rs780180674
• NM_001288590.2:c.527C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001288590.2(ZKSCAN7):​c.527C>G​(p.Ala176Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: ZKSCAN7 NM_001288590.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0570
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.039910764).

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.527C>G	p.Ala176Gly	missense	Exon 3 of 6	NP_001275519.1	Q9P0L1-1
	ZKSCAN7	NM_018651.4		c.527C>G	p.Ala176Gly	missense	Exon 3 of 6	NP_061121.2
	ZKSCAN7	NM_001288592.2		c.77C>G	p.Ala26Gly	missense	Exon 2 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.527C>G	p.Ala176Gly	missense	Exon 3 of 6	ENSP00000395524.1	Q9P0L1-1
	ZKSCAN7	ENST00000273320.7	TSL:1	c.527C>G	p.Ala176Gly	missense	Exon 3 of 6	ENSP00000273320.3	Q9P0L1-1
	ZKSCAN7	ENST00000447279.2	TSL:1	c.77C>G	p.Ala26Gly	missense	Exon 2 of 6	ENSP00000405034.1	C9J6L6

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460306 Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 4 AN XY: 726354

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.000113 AC: 5 AN: 44376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 85682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111478

Other (OTH) AF: 0.0000663 AC: 4 AN: 60364

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.000523 AC: 8 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000238

ExAC AF: 0.0000165 AC: 2

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	0.088
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.0
DANN	Benign	0.62
DEOGEN2	Benign	0.064	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.094	N
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.057
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.015
Sift	Benign	0.34	T
Sift4G	Benign	0.33	T
Polyphen		0.018	B
Vest4		0.13
MutPred		0.16		Loss of sheet (P = 0.1398)
MVP		0.12
MPC		0.066
ClinPred		0.064	T
GERP RS		-0.95
PromoterAI		0.015	Neutral
Varity_R		0.029
gMVP		0.078
Mutation Taster		=99/1	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

dbSNP: rs780180674; hg19: chr3-44607082;