chr19-56384679-C-A

Position:

• chr19-56384679-C-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.738G>T​(p.Gln246His) 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. 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)
• Consequence: ZNF582 NM_001320371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0750

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=0.18163139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF582	NM_001320371.4	c.738G>T	p.Gln246His	missense_variant	5/5	ENST00000586929.6	NP_001307300.2
ZNF582	NM_144690.3	c.738G>T	p.Gln246His	missense_variant	5/5		NP_653291.1
ZNF582	XR_007066621.1	n.911G>T		non_coding_transcript_exon_variant	5/6
ZNF582	XR_430188.4	n.1133G>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.738G>T	p.Gln246His	missense_variant	5/5	1	NM_001320371.4	ENSP00000465619	P1
ZNF582	ENST00000301310.8	c.738G>T	p.Gln246His	missense_variant	5/5	1		ENSP00000301310	P1
ZNF582	ENST00000589143.5	c.232+5322G>T		intron_variant		5		ENSP00000468679
ZNF582	ENST00000589895.2	c.232+5322G>T		intron_variant		2		ENSP00000465639

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Jun 21, 2023

The c.738G>T (p.Q246H) alteration is located in exon 5 (coding exon 4) of the ZNF582 gene. This alteration results from a G to T substitution at nucleotide position 738, causing the glutamine (Q) at amino acid position 246 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	Uncertain	0.49
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.18	.;T;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.9	D;.;.
REVEL	Benign	0.067
Sift	Benign	0.096	T;.;.
Sift4G	Benign	0.074	T;T;T
Polyphen		0.98	D;D;D
Vest4		0.18
MutPred		0.52		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP		0.20
MPC		0.58
ClinPred		0.72	D
GERP RS		1.5
Varity_R		0.17
gMVP		0.31

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: chr19-56896048;