19-44235301-C-T

Variant names:

• chr19-44235301-C-T
• NM_182490.3:c.871C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182490.3(ZNF227):​c.871C>T​(p.His291Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF227 NM_182490.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98
• Publications: 0 publications found

Genes affected

ZNF227 (HGNC:13020): (zinc finger protein 227) Predicted to enable DNA-binding transcription activator 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 act upstream of or within negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF235 (HGNC:12866): (zinc finger protein 235) This gene product belongs to the zinc finger protein superfamily, members of which are regulatory proteins characterized by nucleic acid-binding zinc finger domains. The encoded protein is a member of the Kruppel family of zinc finger proteins, and contains Kruppel-associated box (KRAB) A and B domains and 15 tandemly arrayed C2H2-type zinc fingers. It is an ortholog of the mouse Zfp93 protein. This gene is located in a cluster of zinc finger genes on 19q13.2. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19308075).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182490.3. 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
	ZNF227	NM_182490.3	MANE Select	c.871C>T	p.His291Tyr	missense	Exon 6 of 6	NP_872296.1	Q86WZ6-1
	ZNF227	NM_001289166.2		c.871C>T	p.His291Tyr	missense	Exon 6 of 6	NP_001276095.1	Q86WZ6-1
	ZNF227	NM_001289173.2		c.787C>T	p.His263Tyr	missense	Exon 5 of 5	NP_001276102.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF227	ENST00000313040.12	TSL:1 MANE Select	c.871C>T	p.His291Tyr	missense	Exon 6 of 6	ENSP00000321049.6	Q86WZ6-1
	ZNF227	ENST00000621083.4	TSL:2	c.871C>T	p.His291Tyr	missense	Exon 6 of 6	ENSP00000482749.1	Q86WZ6-1
	ZNF227	ENST00000876872.1		c.871C>T	p.His291Tyr	missense	Exon 6 of 6	ENSP00000546931.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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	Benign	0.069
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		3.0
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.18
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.013	D
Polyphen		0.98	D
Vest4		0.15
MutPred		0.35		Loss of ubiquitination at K295 (P = 0.1)
MVP		0.43
MPC		0.11
ClinPred		0.83	D
GERP RS		4.3
Varity_R		0.13
gMVP		0.12
Mutation Taster		=82/18	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

hg19: chr19-44739454;