19-20118089-G-T

Variant names:

• chr19-20118089-G-T
• rs781797183
• NM_007138.2:c.535G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_007138.2(ZNF90):​c.535G>T​(p.Gly179Cys) variant causes a missense change. 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. G179S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF90 NM_007138.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.02
• Publications: 0 publications found

Genes affected

ZNF90 (HGNC:13165): (zinc finger protein 90) Predicted to enable DNA-binding transcription factor 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF90	NM_007138.2	c.535G>T	p.Gly179Cys	missense_variant	Exon 4 of 4	ENST00000418063.3	NP_009069.1
ZNF90	XM_047439360.1	c.307G>T	p.Gly103Cys	missense_variant	Exon 2 of 2		XP_047295316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF90	ENST00000418063.3	c.535G>T	p.Gly179Cys	missense_variant	Exon 4 of 4	1	NM_007138.2	ENSP00000410466.2
ZNF90	ENST00000469078.5	n.227-3133G>T		intron_variant	Intron 3 of 5	5		ENSP00000420111.1
ZNF90	ENST00000474284.1	n.239-6917G>T		intron_variant	Intron 2 of 3	5
ZNF90	ENST00000473524.5	n.*442G>T		downstream_gene_variant		3		ENSP00000418166.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.040	T
M_CAP	Benign	0.0023	T
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		4.0
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Benign	0.11
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.27
MutPred		0.82		Loss of disorder (P = 0.1355);
MVP		0.45
MPC		0.0072
ClinPred		0.99	D
GERP RS		-0.28
Varity_R		0.17
gMVP		0.0070
Mutation Taster		=97/3	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: rs781797183; hg19: chr19-20228898;