19-44175866-G-T

Variant names:

• chr19-44175866-G-T
• rs774175182
• NM_001032373.2:c.604G>T

Variant summary

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

The NM_001032373.2(ZNF226):​c.604G>T​(p.Gly202Cys) 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. 16/22 in silico tools predict a benign 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. G202S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF226 NM_001032373.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39760765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF226	NM_001032373.2	c.604G>T	p.Gly202Cys	missense_variant	Exon 6 of 6	ENST00000337433.10	NP_001027545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF226	ENST00000337433.10	c.604G>T	p.Gly202Cys	missense_variant	Exon 6 of 6	1	NM_001032373.2	ENSP00000336719.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.5
DANN	Benign	0.34
DEOGEN2	Benign	0.0025	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.15	T;.;.
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.69	N;N;N
PhyloP100		-0.25
PrimateAI	Benign	0.23	T
PROVEAN	Benign	1.4	N;.;N
REVEL	Benign	0.099
Sift	Benign	0.19	T;.;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.0070	B;B;B
Vest4		0.22
MutPred		0.78		Gain of methylation at K201 (P = 0.0357);Gain of methylation at K201 (P = 0.0357);Gain of methylation at K201 (P = 0.0357);
MVP		0.41
MPC		0.019
ClinPred		0.042	T
GERP RS		1.6
Varity_R		0.071
gMVP		0.038
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: rs774175182; hg19: chr19-44680019;