19-52155566-C-G

Variant names:

• chr19-52155566-C-G
• NM_001102657.3:c.2117G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001102657.3(ZNF836):​c.2117G>C​(p.Ser706Thr) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF836 NM_001102657.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.02

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055360347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF836	NM_001102657.3	c.2117G>C	p.Ser706Thr	missense_variant	Exon 5 of 5	ENST00000682614.1	NP_001096127.1
ZNF836	XM_011526558.4	c.2117G>C	p.Ser706Thr	missense_variant	Exon 5 of 5		XP_011524860.1
ZNF836	XM_011526559.4	c.2117G>C	p.Ser706Thr	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.2117G>C	p.Ser706Thr	missense_variant	Exon 5 of 5		NM_001102657.3	ENSP00000507838.1
ZNF836	ENST00000597252.5	c.2117G>C	p.Ser706Thr	missense_variant	Exon 5 of 5	2		ENSP00000470239.1
ENSG00000267827	ENST00000594362.1	n.554+4899G>C		intron_variant	Intron 4 of 4	5
ENSG00000267827	ENST00000598982.5	n.494+4899G>C		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2117G>C (p.S706T) alteration is located in exon 5 (coding exon 3) of the ZNF836 gene. This alteration results from a G to C substitution at nucleotide position 2117, causing the serine (S) at amino acid position 706 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.72
DEOGEN2	Benign	0.0085	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.12	T;T
M_CAP	Benign	0.00083	T
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L;.
PhyloP100		-3.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.69	.;N
REVEL	Benign	0.032
Sift	Benign	0.33	.;T
Sift4G	Benign	0.22	T;T
Polyphen		0.0020	B;.
Vest4		0.066
MutPred		0.20		Loss of ubiquitination at K708 (P = 0.0516);Loss of ubiquitination at K708 (P = 0.0516);
MVP		0.076
MPC		0.18
ClinPred		0.062	T
GERP RS		-4.2
Varity_R		0.057
gMVP		0.012
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

Publications

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Other links and lift over

hg19: chr19-52658819;