chr19-20105274-C-G

Variant names:

• chr19-20105274-C-G
• rs2083393008
• NM_007138.2:c.184C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007138.2(ZNF90):​c.184C>G​(p.Pro62Ala) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P62L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF90 NM_007138.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.642
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13006699).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007138.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF90	NM_007138.2	MANE Select	c.184C>G	p.Pro62Ala	missense	Exon 3 of 4	NP_009069.1	Q03938

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF90	ENST00000418063.3	TSL:1 MANE Select	c.184C>G	p.Pro62Ala	missense	Exon 3 of 4	ENSP00000410466.2	Q03938
	ZNF90	ENST00000469078.5	TSL:5	n.184C>G		non_coding_transcript_exon	Exon 3 of 6	ENSP00000420111.1	F8WDJ7
	ZNF90	ENST00000473524.5	TSL:3	n.184C>G		non_coding_transcript_exon	Exon 3 of 5	ENSP00000418166.1	F8WBQ5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.8
DANN	Benign	0.71
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.64
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.042
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.021	D
Polyphen		0.24	B
Vest4		0.20
MutPred		0.51		Loss of methylation at K66 (P = 0.0724)
MVP		0.28
MPC		0.0026
ClinPred		0.29	T
GERP RS		0.54
Varity_R		0.061
gMVP		0.0063
Mutation Taster		=92/8	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: rs2083393008; hg19: chr19-20216083;