chr7-99506426-A-G

Position:

• chr7-99506426-A-G

Variant summary

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

The NM_001318084.1(ZKSCAN5):​c.-275A>G variant causes a 5 prime UTR premature start codon gain 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_001318084.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.971

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=0.09365603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN5	NM_145102.4	c.382A>G	p.Ile128Val	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.382A>G	p.Ile128Val	missense_variant	2/7	1	NM_145102.4	ENSP00000322872.5
ZKSCAN5	ENST00000394170.6	c.382A>G	p.Ile128Val	missense_variant	2/7	1		ENSP00000377725.2
ZKSCAN5	ENST00000451158.5	c.382A>G	p.Ile128Val	missense_variant	2/7	1		ENSP00000392104.1
ZKSCAN5	ENST00000454175.1	n.382A>G		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

Aug 04, 2021

The c.382A>G (p.I128V) alteration is located in exon 2 (coding exon 1) of the ZKSCAN5 gene. This alteration results from a A to G substitution at nucleotide position 382, causing the isoleucine (I) at amino acid position 128 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	0.40
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T;T;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.24	.;.;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.094	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.44	N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.68	N;N;N
REVEL	Benign	0.060
Sift	Benign	0.077	T;T;T
Sift4G	Uncertain	0.021	D;D;D
Polyphen		0.14	B;B;B
Vest4		0.27
MutPred		0.61		Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);
MVP		0.20
MPC		0.35
ClinPred		0.39	T
GERP RS		-0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.041
gMVP		0.30

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: chr7-99104049;