19-20117870-C-T

Variant names:

• chr19-20117870-C-T
• rs185748773
• NM_007138.2:c.316C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_007138.2(ZNF90):​c.316C>T​(p.Arg106Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,609,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: ZNF90 NM_007138.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.629
• Publications: 3 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010197043).
• BP6: Variant 19-20117870-C-T is Benign according to our data. Variant chr19-20117870-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3990082.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF90	NM_007138.2	c.316C>T	p.Arg106Cys	missense_variant	Exon 4 of 4	ENST00000418063.3	NP_009069.1
ZNF90	XM_047439360.1	c.88C>T	p.Arg30Cys	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.316C>T	p.Arg106Cys	missense_variant	Exon 4 of 4	1	NM_007138.2	ENSP00000410466.2

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 7 AN: 151986 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000115 AC: 28 AN: 242956 AF XY: 0.000144

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00128

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000366

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.0000350 AC: 51 AN: 1457770 Hom.: 0 Cov.: 34 AF XY: 0.0000414 AC XY: 30 AN XY: 724976

African (AFR) AF: 0.00 AC: 0 AN: 33324

American (AMR) AF: 0.00 AC: 0 AN: 43734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.000834 AC: 33 AN: 39576

South Asian (SAS) AF: 0.0000467 AC: 4 AN: 85742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00000811 AC: 9 AN: 1110082

Other (OTH) AF: 0.0000830 AC: 5 AN: 60256

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152106 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41482

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000908 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 06, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.2
DANN	Benign	0.033
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00032	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.00098	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-3.3	N
PhyloP100		-0.63
PrimateAI	Benign	0.30	T
PROVEAN	Benign	6.3	N
REVEL	Benign	0.023
Sift	Benign	1.0	T
Sift4G	Benign	0.38	T
Polyphen		0.0030	B
Vest4		0.045
MVP		0.25
MPC		0.0019
ClinPred		0.017	T
GERP RS		-1.6
Varity_R		0.068
gMVP		0.013
Mutation Taster		=99/1	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: rs185748773; hg19: chr19-20228679;