19-52155080-C-G

Variant names:

• chr19-52155080-C-G
• NM_001102657.3:c.2603G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001102657.3(ZNF836):​c.2603G>C​(p.Gly868Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF836 NM_001102657.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.214

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF836	NM_001102657.3	c.2603G>C	p.Gly868Ala	missense_variant	Exon 5 of 5	ENST00000682614.1	NP_001096127.1
ZNF836	XM_011526558.4	c.2603G>C	p.Gly868Ala	missense_variant	Exon 5 of 5		XP_011524860.1
ZNF836	XM_011526559.4	c.2603G>C	p.Gly868Ala	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.2603G>C	p.Gly868Ala	missense_variant	Exon 5 of 5		NM_001102657.3	ENSP00000507838.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2603G>C (p.G868A) 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 2603, causing the glycine (G) at amino acid position 868 to be replaced by an alanine (A). 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	Uncertain	0.53
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.37	T;T
M_CAP	Benign	0.00086	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.4	.;D
REVEL	Benign	0.071
Sift	Uncertain	0.0040	.;D
Sift4G	Uncertain	0.015	D;D
Polyphen		1.0	D;.
Vest4		0.17
MutPred		0.81		Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);
MVP		0.20
MPC		0.62
ClinPred		0.92	D
GERP RS		-0.87
Varity_R		0.28
gMVP		0.015

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-52658333;