chr7-99512567-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZKSCAN5 NM_145102.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.865
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145102.4. 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
	ZKSCAN5	NM_145102.4	MANE Select	c.529A>G	p.Lys177Glu	missense	Exon 3 of 7	NP_659570.1	Q9Y2L8
	ZKSCAN5	NM_001318082.2		c.529A>G	p.Lys177Glu	missense	Exon 3 of 7	NP_001305011.1	Q9Y2L8
	ZKSCAN5	NM_014569.4		c.529A>G	p.Lys177Glu	missense	Exon 3 of 7	NP_055384.1	Q9Y2L8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZKSCAN5	ENST00000326775.10	TSL:1 MANE Select	c.529A>G	p.Lys177Glu	missense	Exon 3 of 7	ENSP00000322872.5	Q9Y2L8
	ZKSCAN5	ENST00000394170.6	TSL:1	c.529A>G	p.Lys177Glu	missense	Exon 3 of 7	ENSP00000377725.2	Q9Y2L8
	ZKSCAN5	ENST00000451158.5	TSL:1	c.529A>G	p.Lys177Glu	missense	Exon 3 of 7	ENSP00000392104.1	Q9Y2L8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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	0.16
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	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
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.79	N
PhyloP100		0.86
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.022
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.19
MutPred		0.24		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
Mutation Taster		=87/13	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

hg19: chr7-99110190;