7-99506397-G-T

Position:

• chr7-99506397-G-T

Variant summary

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

The NM_145102.4(ZKSCAN5):​c.353G>T​(p.Gly118Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZKSCAN5 NM_145102.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.05

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN5	NM_145102.4	c.353G>T	p.Gly118Val	missense_variant	2/7	ENST00000326775.10	NP_659570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZKSCAN5	ENST00000326775.10	c.353G>T	p.Gly118Val	missense_variant	2/7	1	NM_145102.4	ENSP00000322872.5
ZKSCAN5	ENST00000394170.6	c.353G>T	p.Gly118Val	missense_variant	2/7	1		ENSP00000377725.2
ZKSCAN5	ENST00000451158.5	c.353G>T	p.Gly118Val	missense_variant	2/7	1		ENSP00000392104.1
ZKSCAN5	ENST00000454175.1	n.353G>T		non_coding_transcript_exon_variant	1/5	1		ENSP00000405716.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Apr 15, 2024

The c.353G>T (p.G118V) alteration is located in exon 2 (coding exon 1) of the ZKSCAN5 gene. This alteration results from a G to T substitution at nucleotide position 353, causing the glycine (G) at amino acid position 118 to be replaced by a valine (V). 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	Uncertain	0.54
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.63	.;.;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.8	D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.60
MutPred		0.65		Loss of glycosylation at S117 (P = 0.0417);Loss of glycosylation at S117 (P = 0.0417);Loss of glycosylation at S117 (P = 0.0417);
MVP		0.60
MPC		1.0
ClinPred		0.97	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.51
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-99104020;