7-99512567-A-G

Variant names:

• chr7-99512567-A-G
• NM_145102.4:c.529A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145102.4(ZKSCAN5):​c.529A>G​(p.Lys177Glu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZKSCAN5 NM_145102.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.865

Genes affected

ZKSCAN5 (HGNC:12867): (zinc finger with KRAB and SCAN domains 5) This gene encodes a zinc finger protein of the Kruppel family. The protein contains a SCAN box and a KRAB A domain and may be involved in transcriptional regulation. A similar protein in mouse is differentially expressed in spermatogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03828898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZKSCAN5	NM_145102.4	c.529A>G	p.Lys177Glu	missense_variant	Exon 3 of 7	ENST00000326775.10	NP_659570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZKSCAN5	ENST00000326775.10	c.529A>G	p.Lys177Glu	missense_variant	Exon 3 of 7	1	NM_145102.4	ENSP00000322872.5
ZKSCAN5	ENST00000394170.6	c.529A>G	p.Lys177Glu	missense_variant	Exon 3 of 7	1		ENSP00000377725.2
ZKSCAN5	ENST00000451158.5	c.529A>G	p.Lys177Glu	missense_variant	Exon 3 of 7	1		ENSP00000392104.1
ZKSCAN5	ENST00000454175.1	n.529A>G		non_coding_transcript_exon_variant	Exon 2 of 5	1		ENSP00000405716.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.529A>G (p.K177E) alteration is located in exon 3 (coding exon 2) of the ZKSCAN5 gene. This alteration results from a A to G substitution at nucleotide position 529, causing the lysine (K) at amino acid position 177 to be replaced by a glutamic acid (E). 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	0.16
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.60	.;.;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.038	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.79	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.35	N;N;N
REVEL	Benign	0.022
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.19
MutPred		0.24		Loss of ubiquitination at K177 (P = 0.0012);Loss of ubiquitination at K177 (P = 0.0012);Loss of ubiquitination at K177 (P = 0.0012);
MVP		0.17
MPC		0.34
ClinPred		0.074	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.048
gMVP		0.11

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: chr7-99110190;