rs369202646

Variant names:

• chr19-52155293-C-G
• rs369202646
• NM_001102657.3:c.2390G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-52155293-C-G
• chr19-52155293-C-T

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.2390G>C​(p.Arg797Pro) 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. 13/22 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. R797Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF836 NM_001102657.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 0 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=0.24401647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF836	NM_001102657.3	c.2390G>C	p.Arg797Pro	missense_variant	Exon 5 of 5	ENST00000682614.1	NP_001096127.1
ZNF836	XM_011526558.4	c.2390G>C	p.Arg797Pro	missense_variant	Exon 5 of 5		XP_011524860.1
ZNF836	XM_011526559.4	c.2390G>C	p.Arg797Pro	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.2390G>C	p.Arg797Pro	missense_variant	Exon 5 of 5		NM_001102657.3	ENSP00000507838.1
ZNF836	ENST00000597252.5	c.2390G>C	p.Arg797Pro	missense_variant	Exon 5 of 5	2		ENSP00000470239.1
ENSG00000267827	ENST00000594362.1	n.554+5172G>C		intron_variant	Intron 4 of 4	5
ENSG00000267827	ENST00000598982.5	n.494+5172G>C		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.35	T;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.
PhyloP100		-1.7
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-2.6	.;D
REVEL	Benign	0.063
Sift	Uncertain	0.021	.;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.94	P;.
Vest4		0.26
MutPred		0.58		Loss of MoRF binding (P = 0.0053);Loss of MoRF binding (P = 0.0053);
MVP		0.25
MPC		0.53
ClinPred		0.83	D
GERP RS		0.71
Varity_R		0.28
gMVP		0.26
Mutation Taster		=97/3	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: rs369202646; hg19: chr19-52658546;