chr19-56384842-A-C

Position:

• chr19-56384842-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001320371.4(ZNF582):​c.575T>G​(p.Ile192Ser) 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: 33)
• Consequence: ZNF582 NM_001320371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25

Genes affected

ZNF582 (HGNC:26421): (zinc finger protein 582) The protein encoded by this gene is a zing finger protein and putative transcription factor that is highly methylated in cervical cancers. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35969543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF582	NM_001320371.4	c.575T>G	p.Ile192Ser	missense_variant	5/5	ENST00000586929.6	NP_001307300.2
ZNF582	NM_144690.3	c.575T>G	p.Ile192Ser	missense_variant	5/5		NP_653291.1
ZNF582	XR_007066621.1	n.748T>G		non_coding_transcript_exon_variant	5/6
ZNF582	XR_430188.4	n.970T>G		non_coding_transcript_exon_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF582	ENST00000586929.6	c.575T>G	p.Ile192Ser	missense_variant	5/5	1	NM_001320371.4	ENSP00000465619	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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 03, 2024

The c.575T>G (p.I192S) alteration is located in exon 5 (coding exon 4) of the ZNF582 gene. This alteration results from a T to G substitution at nucleotide position 575, causing the isoleucine (I) at amino acid position 192 to be replaced by a serine (S). 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	0.17
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.39	.;T;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.79	N;N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-4.3	D;.;.
REVEL	Benign	0.19
Sift	Uncertain	0.012	D;.;.
Sift4G	Uncertain	0.024	D;D;D
Polyphen		0.82	P;P;P
Vest4		0.50
MutPred		0.66		Gain of disorder (P = 0.0108);Gain of disorder (P = 0.0108);Gain of disorder (P = 0.0108);
MVP		0.14
MPC		0.22
ClinPred		0.38	T
GERP RS		3.8
Varity_R		0.36
gMVP		0.19

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: chr19-56896211;