19-20118089-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007138.2(ZNF90):​c.535G>C​(p.Gly179Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,332 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF90	NM_007138.2	c.535G>C	p.Gly179Arg	missense_variant	Exon 4 of 4	ENST00000418063.3	NP_009069.1
ZNF90	XM_047439360.1	c.307G>C	p.Gly103Arg	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>C	p.Gly179Arg	missense_variant	Exon 4 of 4	1	NM_007138.2	ENSP00000410466.2
ZNF90	ENST00000469078.5	n.227-3133G>C		intron_variant	Intron 3 of 5	5		ENSP00000420111.1
ZNF90	ENST00000474284.1	n.239-6917G>C		intron_variant	Intron 2 of 3	5
ZNF90	ENST00000473524.5	n.*442G>C		downstream_gene_variant		3		ENSP00000418166.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461332 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726902

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111732

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0020	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.0
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.11
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.024	D
Polyphen		1.0	D
Vest4		0.20
MutPred		0.77		Gain of MoRF binding (P = 0.0365);
MVP		0.41
MPC		0.0064
ClinPred		0.95	D
GERP RS		-0.28
Varity_R		0.073
gMVP		0.0051
Mutation Taster		=99/1	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: rs781797183; hg19: chr19-20228898;