chr19-20934957-G-T

Variant names:

• chr19-20934957-G-T
• rs756638820
• NM_003429.5:c.139G>T

Variant summary

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

The NM_003429.5(ZNF85):​c.139G>T​(p.Val47Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. V47I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF85 NM_003429.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• 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 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
ZNF85	NM_003429.5	c.139G>T	p.Val47Phe	missense_variant	Exon 3 of 4	ENST00000328178.13	NP_003420.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF85	ENST00000328178.13	c.139G>T	p.Val47Phe	missense_variant	Exon 3 of 4	1	NM_003429.5	ENSP00000329793.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453440 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 722772

African (AFR) AF: 0.00 AC: 0 AN: 33228

American (AMR) AF: 0.00 AC: 0 AN: 43972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25868

East Asian (EAS) AF: 0.00 AC: 0 AN: 39468

South Asian (SAS) AF: 0.00 AC: 0 AN: 84286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107982

Other (OTH) AF: 0.00 AC: 0 AN: 59992

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.073	.;.;.;T;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.030	T;T;T;T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.94	L;.;.;L;.
PhyloP100		-0.038
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-4.5	D;.;.;D;.
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D;.;.;T;.
Sift4G	Benign	0.095	T;D;T;T;T
Polyphen		0.0010	.;.;.;B;.
Vest4		0.23
MutPred		0.42		Gain of ubiquitination at K49 (P = 0.0954);Gain of ubiquitination at K49 (P = 0.0954);Gain of ubiquitination at K49 (P = 0.0954);Gain of ubiquitination at K49 (P = 0.0954);.;
MVP		0.12
MPC		0.011
ClinPred		0.13	T
GERP RS		1.1
Varity_R		0.12
gMVP		0.029
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.38		Position offset: 13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs756638820; hg19: chr19-21117763;