3-44557090-A-T

Variant names:

• chr3-44557090-A-T
• NM_001288590.2:c.43A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001288590.2(ZKSCAN7):​c.43A>T​(p.Ser15Cys) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S15N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZKSCAN7 NM_001288590.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.241
• Publications: 0 publications found

Genes affected

ZKSCAN7 (HGNC:12955): (zinc finger with KRAB and SCAN domains 7) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZKSCAN7-AS1 (HGNC:53964): (ZKSCAN7 ZNF cluster antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.102929324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZKSCAN7	NM_001288590.2	c.43A>T	p.Ser15Cys	missense_variant	Exon 2 of 6	ENST00000426540.6	NP_001275519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZKSCAN7	ENST00000426540.6	c.43A>T	p.Ser15Cys	missense_variant	Exon 2 of 6	2	NM_001288590.2	ENSP00000395524.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.43A>T (p.S15C) alteration is located in exon 2 (coding exon 1) of the ZKSCAN7 gene. This alteration results from a A to T substitution at nucleotide position 43, causing the serine (S) at amino acid position 15 to be replaced by a cysteine (C). 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	0.088
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.086	T;.;.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.094	N
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M;M;M;M
PhyloP100		0.24
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.053
Sift	Benign	0.072	T;D;D;T
Sift4G	Benign	0.085	T;T;T;T
Polyphen		0.68	P;P;P;P
Vest4		0.25
MutPred		0.32		Loss of disorder (P = 0.0143);Loss of disorder (P = 0.0143);Loss of disorder (P = 0.0143);Loss of disorder (P = 0.0143);
MVP		0.28
MPC		0.17
ClinPred		0.10	T
GERP RS		-1.4
Varity_R		0.074
gMVP		0.21
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr3-44598582;