rs200158862

Variant names:

• chr19-52155074-G-A
• rs200158862
• NM_001102657.3:c.2609C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-52155074-G-A
• chr19-52155074-G-C

Variant summary

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

The NM_001102657.3(ZNF836):​c.2609C>T​(p.Ala870Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 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. 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. A870G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF836 NM_001102657.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 3 publications found

Genes affected

ZNF836 (HGNC:34333): (zinc finger protein 836) Predicted to enable DNA-binding transcription activator 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267827 (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=0.14196563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF836	NM_001102657.3	c.2609C>T	p.Ala870Val	missense_variant	Exon 5 of 5	ENST00000682614.1	NP_001096127.1
ZNF836	XM_011526558.4	c.2609C>T	p.Ala870Val	missense_variant	Exon 5 of 5		XP_011524860.1
ZNF836	XM_011526559.4	c.2609C>T	p.Ala870Val	missense_variant	Exon 4 of 4		XP_011524861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF836	ENST00000682614.1	c.2609C>T	p.Ala870Val	missense_variant	Exon 5 of 5		NM_001102657.3	ENSP00000507838.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111992

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.30	T;T
M_CAP	Benign	0.00086	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
PhyloP100		-1.0
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	.;N
REVEL	Benign	0.034
Sift	Benign	0.37	.;T
Sift4G	Benign	0.13	T;T
Polyphen		0.99	D;.
Vest4		0.20
MutPred		0.47		Loss of catalytic residue at A870 (P = 0.0235);Loss of catalytic residue at A870 (P = 0.0235);
MVP		0.13
MPC		0.59
ClinPred		0.37	T
GERP RS		-0.51
Varity_R		0.035
gMVP		0.0077
Mutation Taster		=100/0	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: rs200158862; hg19: chr19-52658327;