chr19-56384685-T-A

Position:

• chr19-56384685-T-A

Variant summary

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

The NM_001320371.4(ZNF582):​c.732A>T​(p.Gln244His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF582 NM_001320371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -7.95

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093958646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF582	NM_001320371.4	c.732A>T	p.Gln244His	missense_variant	5/5	ENST00000586929.6	NP_001307300.2
ZNF582	NM_144690.3	c.732A>T	p.Gln244His	missense_variant	5/5		NP_653291.1
ZNF582	XR_007066621.1	n.905A>T		non_coding_transcript_exon_variant	5/6
ZNF582	XR_430188.4	n.1127A>T		non_coding_transcript_exon_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF582	ENST00000586929.6	c.732A>T	p.Gln244His	missense_variant	5/5	1	NM_001320371.4	ENSP00000465619	P1
ZNF582	ENST00000301310.8	c.732A>T	p.Gln244His	missense_variant	5/5	1		ENSP00000301310	P1
ZNF582	ENST00000589143.5	c.232+5316A>T		intron_variant		5		ENSP00000468679
ZNF582	ENST00000589895.2	c.232+5316A>T		intron_variant		2		ENSP00000465639

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461220 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726878

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jul 20, 2022

The c.732A>T (p.Q244H) alteration is located in exon 5 (coding exon 4) of the ZNF582 gene. This alteration results from a A to T substitution at nucleotide position 732, causing the glutamine (Q) at amino acid position 244 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	Pathogenic	0.83
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.20	.;T;.
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.094	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.9	D;.;.
REVEL	Benign	0.070
Sift	Benign	0.034	D;.;.
Sift4G	Benign	0.13	T;T;T
Polyphen		0.42	B;B;B
Vest4		0.15
MutPred		0.35		Gain of catalytic residue at Q244 (P = 0.1307);Gain of catalytic residue at Q244 (P = 0.1307);Gain of catalytic residue at Q244 (P = 0.1307);
MVP		0.088
MPC		0.58
ClinPred		0.61	D
GERP RS		-3.9
Varity_R		0.18
gMVP		0.16

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: chr19-56896054;