7-99506219-C-T

Variant names:

• chr7-99506219-C-T
• NM_145102.4:c.175C>T

Variant summary

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

The NM_145102.4(ZKSCAN5):​c.175C>T​(p.His59Tyr) 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. 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: 0.426

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2347337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZKSCAN5	NM_145102.4	c.175C>T	p.His59Tyr	missense_variant	Exon 2 of 7	ENST00000326775.10	NP_659570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZKSCAN5	ENST00000326775.10	c.175C>T	p.His59Tyr	missense_variant	Exon 2 of 7	1	NM_145102.4	ENSP00000322872.5
ZKSCAN5	ENST00000394170.6	c.175C>T	p.His59Tyr	missense_variant	Exon 2 of 7	1		ENSP00000377725.2
ZKSCAN5	ENST00000451158.5	c.175C>T	p.His59Tyr	missense_variant	Exon 2 of 7	1		ENSP00000392104.1
ZKSCAN5	ENST00000454175.1	n.175C>T		non_coding_transcript_exon_variant	Exon 1 of 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

Jan 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.175C>T (p.H59Y) alteration is located in exon 2 (coding exon 1) of the ZKSCAN5 gene. This alteration results from a C to T substitution at nucleotide position 175, causing the histidine (H) at amino acid position 59 to be replaced by a tyrosine (Y). 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	0.24
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.27	.;.;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N;N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.077
Sift	Benign	0.058	T;T;T
Sift4G	Benign	0.42	T;T;T
Polyphen		0.84	P;P;P
Vest4		0.22
MutPred		0.62		Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);
MVP		0.36
MPC		0.31
ClinPred		0.42	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.18
gMVP		0.57

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: chr7-99103842;