1-26170125-A-C

Position:

• chr1-26170125-A-C

Variant summary

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

The NM_015871.5(ZNF593):​c.142A>C​(p.Asn48His) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ZNF593 NM_015871.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0940

Genes affected

ZNF593 (HGNC:30943): (zinc finger protein 593) Enables zinc ion binding activity. Involved in negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding activity and positive regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF593OS (HGNC:41278): (ZNF593 opposite strand)

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=0.08896357).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF593	NM_015871.5	c.142A>C	p.Asn48His	missense_variant	1/3	ENST00000374266.7	NP_056955.2
ZNF593OS	NM_001395468.1	c.*507T>G		3_prime_UTR_variant	4/4	ENST00000433939.7	NP_001382397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF593	ENST00000374266.7	c.142A>C	p.Asn48His	missense_variant	1/3	1	NM_015871.5	ENSP00000363384	P1
ZNF593OS	ENST00000433939.7	c.*507T>G		3_prime_UTR_variant	4/4	3	NM_001395468.1	ENSP00000489416	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

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

Jan 23, 2023

The c.142A>C (p.N48H) alteration is located in exon 1 (coding exon 1) of the ZNF593 gene. This alteration results from a A to C substitution at nucleotide position 142, causing the asparagine (N) at amino acid position 48 to be replaced by a histidine (H). 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	0.063
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.4
DANN	Benign	0.88
DEOGEN2	Benign	0.021	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.089	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.73	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.046
Sift	Benign	0.15	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.042	B;.
Vest4		0.22
MutPred		0.13		Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);
MVP		0.21
MPC		0.63
ClinPred		0.087	T
GERP RS		0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.086
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-26496616;