rs1273775236

Variant names:

• chr19-20948770-C-A
• rs1273775236
• NM_003429.5:c.256C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-20948770-C-A
• chr19-20948770-C-G

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.256C>A​(p.Leu86Ile) 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. L86V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF85 NM_003429.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• 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=0.1026409).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF85	NM_003429.5	c.256C>A	p.Leu86Ile	missense_variant	Exon 4 of 4	ENST00000328178.13	NP_003420.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF85	ENST00000328178.13	c.256C>A	p.Leu86Ile	missense_variant	Exon 4 of 4	1	NM_003429.5	ENSP00000329793.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.2
DANN	Benign	0.92
DEOGEN2	Benign	0.014	.;.;T;.;.;.;.;.;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.67	T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.00083	T
MetaRNN	Benign	0.10	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	.;.;M;.;.;.;.;.;.
PhyloP100		-0.0010
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	.;.;N;.;N;.;.;.;.
REVEL	Benign	0.038
Sift	Benign	0.074	.;.;T;.;D;.;.;.;.
Sift4G	Benign	0.17	T;D;T;T;T;T;T;T;T
Polyphen		0.79, 0.64	.;.;P;.;P;.;.;.;.
Vest4		0.15, 0.23
MutPred		0.29		.;.;Gain of catalytic residue at P88 (P = 0.0281);.;.;.;.;.;.;
MVP		0.16
MPC		0.011
ClinPred		0.20	T
GERP RS		-0.84
Varity_R		0.075
gMVP		0.0088
Mutation Taster		=98/2	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: rs1273775236; hg19: chr19-21131576;