19-20934096-C-T

Variant names:

• chr19-20934096-C-T
• rs201139670
• NM_003429.5:c.76C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003429.5(ZNF85):​c.76C>T​(p.Arg26Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,612,106 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R26Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000060 (0 hom.)
• Consequence: ZNF85 NM_003429.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.137
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26842925).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003429.5. 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
	ZNF85	NM_003429.5	MANE Select	c.76C>T	p.Arg26Trp	missense	Exon 2 of 4	NP_003420.2	Q03923-1
	ZNF85	NM_001256171.2		c.76C>T	p.Arg26Trp	missense	Exon 2 of 5	NP_001243100.1
	ZNF85	NM_001256172.2		c.76C>T	p.Arg26Trp	missense	Exon 2 of 4	NP_001243101.1	Q03923-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF85	ENST00000328178.13	TSL:1 MANE Select	c.76C>T	p.Arg26Trp	missense	Exon 2 of 4	ENSP00000329793.7	Q03923-1
	ZNF85	ENST00000300540.7	TSL:1	c.76C>T	p.Arg26Trp	missense	Exon 2 of 4	ENSP00000300540.2	Q03923-3
	ZNF85	ENST00000596476.1	TSL:1	c.-21C>T		5_prime_UTR	Exon 2 of 4	ENSP00000469496.1	Q96HE0

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151798 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251276 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000596 AC: 87 AN: 1460308 Hom.: 0 Cov.: 32 AF XY: 0.0000551 AC XY: 40 AN XY: 726492

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53090

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

European-Non Finnish (NFE) AF: 0.0000702 AC: 78 AN: 1111132

Other (OTH) AF: 0.000116 AC: 7 AN: 60310

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151798 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74102

African (AFR) AF: 0.0000242 AC: 1 AN: 41288

American (AMR) AF: 0.00 AC: 0 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10532

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000607 Hom.: 0

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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	0.16
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.84
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.14
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.072
Sift	Benign	0.060	T
Sift4G	Benign	0.13	T
Polyphen		0.047	B
Vest4		0.23
MutPred		0.71		Gain of catalytic residue at D22 (P = 0.2386)
MVP		0.32
MPC		0.0043
ClinPred		0.095	T
GERP RS		-0.81
Varity_R		0.095
gMVP		0.30
Mutation Taster		=96/4	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: rs201139670; hg19: chr19-21116902;