chr1-26170093-C-T

Position:

• chr1-26170093-C-T

Variant summary

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

The NM_015871.5(ZNF593):​c.110C>T​(p.Pro37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 1,419,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: ZNF593 NM_015871.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67

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=0.17943129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF593	NM_015871.5	c.110C>T	p.Pro37Leu	missense_variant	1/3	ENST00000374266.7
ZNF593OS	NM_001395468.1	c.*539G>A		3_prime_UTR_variant	4/4	ENST00000433939.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF593	ENST00000374266.7	c.110C>T	p.Pro37Leu	missense_variant	1/3	1	NM_015871.5	P1
ZNF593OS	ENST00000433939.7	c.*539G>A		3_prime_UTR_variant	4/4	3	NM_001395468.1	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000352 AC: 5 AN: 1419224 Hom.: 0 Cov.: 33 AF XY: 0.00000569 AC XY: 4 AN XY: 702674

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000457

Gnomad4 OTH exome AF: 0.00

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

Mar 11, 2024

The c.110C>T (p.P37L) alteration is located in exon 1 (coding exon 1) of the ZNF593 gene. This alteration results from a C to T substitution at nucleotide position 110, causing the proline (P) at amino acid position 37 to be replaced by a leucine (L). 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	0.094
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.70	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.0	M;.
MutationTaster	Benign	0.65	D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-6.4	D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D;D
Sift4G	Benign	0.10	T;T
Polyphen		0.0010	B;.
Vest4		0.21
MutPred		0.18		Gain of MoRF binding (P = 0.0678);Gain of MoRF binding (P = 0.0678);
MVP		0.20
MPC		0.65
ClinPred		0.70	D
GERP RS		3.8
Varity_R		0.42
gMVP		0.63

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

LitVar

Other links and lift over

dbSNP: rs1043344394; hg19: chr1-26496584;