NM_003429.5:c.202C>A

Variant names:

• chr19-20935020-C-A
• rs1555793623
• NM_003429.5:c.202C>A

Variant summary

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

The NM_003429.5(ZNF85):​c.202C>A​(p.His68Asn) 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. 15/22 in silico tools predict 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. H68Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF85 NM_003429.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079679966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF85	NM_003429.5	c.202C>A	p.His68Asn	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.202C>A	p.His68Asn	missense_variant	Exon 3 of 4	1	NM_003429.5	ENSP00000329793.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.1
DANN	Benign	0.53
DEOGEN2	Benign	0.078	.;.;.;.;T;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.033	T;T;T;T;T;T;T
M_CAP	Benign	0.00095	T
MetaRNN	Benign	0.080	T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.52	.;N;.;.;N;.;.
PhyloP100		-0.58
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-6.1	.;D;.;.;D;.;.
REVEL	Benign	0.033
Sift	Benign	0.16	.;T;.;.;T;.;.
Sift4G	Benign	0.24	T;T;T;T;T;T;T
Polyphen		0.016	.;.;.;.;B;.;.
Vest4		0.22, 0.20, 0.23
MutPred		0.20		.;Loss of disorder (P = 0.1097);Loss of disorder (P = 0.1097);Loss of disorder (P = 0.1097);Loss of disorder (P = 0.1097);.;.;
MVP		0.12
MPC		0.0079
ClinPred		0.079	T
GERP RS		-2.1
Varity_R		0.12
gMVP		0.010
Mutation Taster		=94/6	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: rs1555793623; hg19: chr19-21117826;