19-44235301-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

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=0.19308075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF227	NM_182490.3	c.871C>T	p.His291Tyr	missense_variant	Exon 6 of 6	ENST00000313040.12	NP_872296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF227	ENST00000313040.12	c.871C>T	p.His291Tyr	missense_variant	Exon 6 of 6	1	NM_182490.3	ENSP00000321049.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.871C>T (p.H291Y) alteration is located in exon 6 (coding exon 4) of the ZNF227 gene. This alteration results from a C to T substitution at nucleotide position 871, causing the histidine (H) at amino acid position 291 to be replaced by a tyrosine (Y). 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	0.069
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	.;T;T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.33	T;T;.;.
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	3.2	.;M;M;.
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.3	D;.;D;.
REVEL	Benign	0.18
Sift	Uncertain	0.012	D;.;T;.
Sift4G	Uncertain	0.013	D;D;D;D
Polyphen		0.98	.;D;D;.
Vest4		0.15
MutPred		0.35		.;Loss of ubiquitination at K295 (P = 0.1);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

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: chr19-44739454;