19-44172109-G-T

Variant names:

• chr19-44172109-G-T
• rs752607335
• NM_001032373.2:c.37G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001032373.2(ZNF226):​c.37G>T​(p.Val13Leu) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V13M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF226 NM_001032373.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF226	NM_001032373.2	c.37G>T	p.Val13Leu	missense_variant	Exon 4 of 6	ENST00000337433.10	NP_001027545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF226	ENST00000337433.10	c.37G>T	p.Val13Leu	missense_variant	Exon 4 of 6	1	NM_001032373.2	ENSP00000336719.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;.;T;.;.;.;.;.;.;.;.;.;.;.;T;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.75	T;.;T;T;T;T;.;.;.;T;D;T;T;T;.;.;T
M_CAP	Benign	0.0070	T
MetaRNN	Pathogenic	0.87	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	.;.;M;.;.;.;.;M;M;M;.;.;.;.;M;M;.
PhyloP100		2.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	.;.;D;.;.;.;.;D;.;D;.;.;.;.;.;D;.
REVEL	Benign	0.22
Sift	Pathogenic	0.0	.;.;D;.;.;.;.;D;.;D;.;.;.;.;.;D;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.96	.;.;D;.;.;.;.;.;.;.;.;.;.;.;D;D;.
Vest4		0.66, 0.46, 0.65, 0.65, 0.46
MutPred		0.80		Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);Gain of ubiquitination at K11 (P = 0.1586);
MVP		0.41
MPC		0.14
ClinPred		0.91	D
GERP RS		2.2
Varity_R		0.31
gMVP		0.20
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs752607335; hg19: chr19-44676262;