19-20934079-G-C

Variant names:

• chr19-20934079-G-C
• rs777283472
• NM_003429.5:c.59G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003429.5(ZNF85):​c.59G>C​(p.Cys20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,612,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: ZNF85 NM_003429.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.783
• Publications: 0 publications found

Genes affected

ZNF85 (HGNC:13160): (zinc finger protein 85) Enables DNA-binding transcription repressor 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. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000298806 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25094086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF85	NM_003429.5	c.59G>C	p.Cys20Ser	missense_variant	Exon 2 of 4	ENST00000328178.13	NP_003420.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF85	ENST00000328178.13	c.59G>C	p.Cys20Ser	missense_variant	Exon 2 of 4	1	NM_003429.5	ENSP00000329793.7

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152012 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251226 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000959 AC: 14 AN: 1460480 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 726550

African (AFR) AF: 0.000389 AC: 13 AN: 33428

American (AMR) AF: 0.0000224 AC: 1 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111260

Other (OTH) AF: 0.00 AC: 0 AN: 60322

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152012 Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9 AN XY: 74256

African (AFR) AF: 0.000363 AC: 15 AN: 41376

American (AMR) AF: 0.0000656 AC: 1 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.0000712 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.59G>C (p.C20S) alteration is located in exon 2 (coding exon 2) of the ZNF85 gene. This alteration results from a G to C substitution at nucleotide position 59, causing the cysteine (C) at amino acid position 20 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.043	.;.;.;.;.;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.054	T;T;T;T;T;T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.25	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;.;L;.;.;L;L
PhyloP100		-0.78
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-9.0	.;.;D;.;.;D;D
REVEL	Benign	0.039
Sift	Uncertain	0.0010	.;.;D;.;.;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;T;T
Polyphen		1.0	.;.;.;.;.;D;.
Vest4		0.32
MutPred		0.58		Gain of disorder (P = 0.0138);Gain of disorder (P = 0.0138);Gain of disorder (P = 0.0138);Gain of disorder (P = 0.0138);Gain of disorder (P = 0.0138);Gain of disorder (P = 0.0138);Gain of disorder (P = 0.0138);
MVP		0.24
MPC		0.015
ClinPred		0.29	T
GERP RS		-0.11
Varity_R		0.53
gMVP		0.057
Mutation Taster		=95/5	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: rs777283472; hg19: chr19-21116885;