3-44568379-A-G

Position:

• chr3-44568379-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001288590.2(ZKSCAN7):​c.757A>G​(p.Arg253Gly) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZKSCAN7 NM_001288590.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.670

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.121658504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN7	NM_001288590.2	c.757A>G	p.Arg253Gly	missense_variant	5/6	ENST00000426540.6	NP_001275519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZKSCAN7	ENST00000426540.6	c.757A>G	p.Arg253Gly	missense_variant	5/6	2	NM_001288590.2	ENSP00000395524.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2021

The c.757A>G (p.R253G) alteration is located in exon 5 (coding exon 4) of the ZKSCAN7 gene. This alteration results from a A to G substitution at nucleotide position 757, causing the arginine (R) at amino acid position 253 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T;.;.;T;T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.47	N
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.2	M;M;M;M;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-4.2	D;D;D;D;D;D
REVEL	Benign	0.069
Sift	Benign	0.051	T;D;D;T;D;D
Sift4G	Uncertain	0.035	D;D;D;D;D;D
Polyphen		0.0	B;B;B;B;.;.
Vest4		0.29
MutPred		0.46		Loss of MoRF binding (P = 0.0274);Loss of MoRF binding (P = 0.0274);Loss of MoRF binding (P = 0.0274);Loss of MoRF binding (P = 0.0274);.;.;
MVP		0.16
MPC		0.086
ClinPred		0.25	T
GERP RS		-1.1
Varity_R		0.19
gMVP		0.33

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-44609871;