19-44172165-G-T

Position:

• chr19-44172165-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001032373.2(ZNF226):​c.93G>T​(p.Lys31Asn) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF226 NM_001032373.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.608

Genes affected

ZNF226 (HGNC:13019): (zinc finger protein 226) 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 be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2904325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF226	NM_001032373.2	c.93G>T	p.Lys31Asn	missense_variant	4/6	ENST00000337433.10	NP_001027545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF226	ENST00000337433.10	c.93G>T	p.Lys31Asn	missense_variant	4/6	1	NM_001032373.2	ENSP00000336719.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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 27, 2024

The c.93G>T (p.K31N) alteration is located in exon 4 (coding exon 2) of the ZNF226 gene. This alteration results from a G to T substitution at nucleotide position 93, causing the lysine (K) at amino acid position 31 to be replaced by an asparagine (N). 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	0.21
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	.;.;T;.;.;.;.;.;.;.;.;.;.;T;T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.068	T;.;T;T;T;T;.;.;.;T;T;T;T;.;.;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.29	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.24	.;.;N;.;.;.;.;N;N;N;.;.;.;N;N;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.6	.;.;D;.;.;.;.;D;.;D;.;.;.;.;D;.
REVEL	Benign	0.083
Sift	Uncertain	0.0050	.;.;D;.;.;.;.;T;.;T;.;.;.;.;D;.
Sift4G	Benign	0.071	T;T;D;T;T;T;T;T;T;T;T;T;T;D;D;T
Polyphen		0.46	.;.;P;.;.;.;.;.;.;.;.;.;.;P;P;.
Vest4		0.37, 0.42, 0.35, 0.36, 0.41
MutPred		0.43		Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);Loss of methylation at K31 (P = 0.0121);
MVP		0.51
MPC		0.057
ClinPred		0.80	D
GERP RS		2.1
Varity_R		0.24
gMVP		0.080

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: chr19-44676318;