NM_001012981.5:c.2317A>T

Variant names:

• chr16-25240403-T-A
• NM_001012981.5:c.2317A>T

Variant summary

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

The NM_001012981.5(ZKSCAN2):​c.2317A>T​(p.Asn773Tyr) 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: ZKSCAN2 NM_001012981.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.27

Genes affected

ZKSCAN2 (HGNC:25677): (zinc finger with KRAB and SCAN domains 2) 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
ZKSCAN2	NM_001012981.5	c.2317A>T	p.Asn773Tyr	missense_variant	Exon 7 of 7	ENST00000328086.12	NP_001012999.3
ZKSCAN2	XM_017023200.3	c.1705A>T	p.Asn569Tyr	missense_variant	Exon 6 of 6		XP_016878689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZKSCAN2	ENST00000328086.12	c.2317A>T	p.Asn773Tyr	missense_variant	Exon 7 of 7	1	NM_001012981.5	ENSP00000331626.7
ZKSCAN2	ENST00000569150.1	n.*1629A>T		non_coding_transcript_exon_variant	Exon 7 of 7	2		ENSP00000455586.1
ZKSCAN2	ENST00000569150.1	n.*1629A>T		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000455586.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2317A>T (p.N773Y) alteration is located in exon 7 (coding exon 7) of the ZKSCAN2 gene. This alteration results from a A to T substitution at nucleotide position 2317, causing the asparagine (N) at amino acid position 773 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	0.20
BayesDel_addAF	Benign	-0.0059	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.18
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.027	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.40		Loss of methylation at K771 (P = 0.0618);
MVP		0.34
MPC		0.64
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.30
gMVP		0.20

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: chr16-25251724;