chr19-57813305-A-T

Variant names:

• chr19-57813305-A-T
• rs372239020
• NM_024762.3:c.149T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024762.3(ZNF552):​c.149T>A​(p.Met50Lys) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF552 NM_024762.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.784
• Publications: 0 publications found

Genes affected

ZNF552 (HGNC:26135): (zinc finger protein 552) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF586 (HGNC:25949): (zinc finger protein 586) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27670753).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024762.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF552	NM_024762.3	MANE Select	c.149T>A	p.Met50Lys	missense	Exon 2 of 3	NP_079038.2	Q9H707

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF552	ENST00000391701.1	TSL:2 MANE Select	c.149T>A	p.Met50Lys	missense	Exon 2 of 3	ENSP00000375582.1	Q9H707
	ZNF552	ENST00000594473.1	TSL:2	c.98T>A	p.Met33Lys	missense	Exon 1 of 2	ENSP00000472459.1	M0R2C3
	ZNF586	ENST00000598885.5	TSL:4	c.164-1121A>T		intron	N/A	ENSP00000470397.1	M0QZ99

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.81
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.78
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.022
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.019	B
Vest4		0.45
MutPred		0.73		Gain of catalytic residue at M50 (P = 0.0049)
MVP		0.23
MPC		0.90
ClinPred		0.13	T
GERP RS		0.76
PromoterAI		0.0081	Neutral
Varity_R		0.38
gMVP		0.35
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs372239020; hg19: chr19-58324673;