7-99512472-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145102.4(ZKSCAN5):​c.434T>C​(p.Val145Ala) 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: 32)

Consequence

ZKSCAN5
NM_145102.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0610
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.055686027).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZKSCAN5NM_145102.4 linkuse as main transcriptc.434T>C p.Val145Ala missense_variant 3/7 ENST00000326775.10 NP_659570.1 Q9Y2L8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZKSCAN5ENST00000326775.10 linkuse as main transcriptc.434T>C p.Val145Ala missense_variant 3/71 NM_145102.4 ENSP00000322872.5 Q9Y2L8
ZKSCAN5ENST00000394170.6 linkuse as main transcriptc.434T>C p.Val145Ala missense_variant 3/71 ENSP00000377725.2 Q9Y2L8
ZKSCAN5ENST00000451158.5 linkuse as main transcriptc.434T>C p.Val145Ala missense_variant 3/71 ENSP00000392104.1 Q9Y2L8
ZKSCAN5ENST00000454175.1 linkuse as main transcriptn.434T>C non_coding_transcript_exon_variant 2/51 ENSP00000405716.1 F8WBD4

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 24, 2023The c.434T>C (p.V145A) alteration is located in exon 3 (coding exon 2) of the ZKSCAN5 gene. This alteration results from a T to C substitution at nucleotide position 434, causing the valine (V) at amino acid position 145 to be replaced by an alanine (A). 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
0.18
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
6.0
DANN
Benign
0.47
DEOGEN2
Benign
0.040
T;T;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.14
.;.;T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.056
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.2
M;M;M
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.72
N;N;N
REVEL
Benign
0.065
Sift
Benign
0.17
T;T;T
Sift4G
Benign
0.80
T;T;T
Polyphen
0.0010
B;B;B
Vest4
0.22
MutPred
0.19
Gain of glycosylation at K149 (P = 0.1654);Gain of glycosylation at K149 (P = 0.1654);Gain of glycosylation at K149 (P = 0.1654);
MVP
0.030
MPC
0.30
ClinPred
0.069
T
GERP RS
-5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.020
gMVP
0.27

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: chr7-99110095; API