19-21727128-T-C

Position:

• chr19-21727128-T-C

Variant summary

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

The NM_173531.4(ZNF100):​c.1184A>G​(p.His395Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF100 NM_173531.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10

Genes affected

ZNF100 (HGNC:12880): (zinc finger protein 100) Predicted to enable DNA-binding transcription factor 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. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	Protein	UniProt
ZNF100	NM_173531.4	c.1184A>G	p.His395Arg	missense_variant	5/5	ENST00000358296.11	NP_775802.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF100	ENST00000358296.11	c.1184A>G	p.His395Arg	missense_variant	5/5	1	NM_173531.4	ENSP00000351042.5
ZNF100	ENST00000305570.10	c.992A>G	p.His331Arg	missense_variant	4/4	1		ENSP00000445201.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2024

The c.1184A>G (p.H395R) alteration is located in exon 5 (coding exon 5) of the ZNF100 gene. This alteration results from a A to G substitution at nucleotide position 1184, causing the histidine (H) at amino acid position 395 to be replaced by an arginine (R). 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	0.41
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T;.;.
Eigen	Benign	0.096
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.31	.;.;T
M_CAP	Benign	0.0041	T
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Uncertain	-0.028	T
MutationAssessor	Uncertain	2.6	M;.;.
PROVEAN	Pathogenic	-7.8	D;D;.
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.32
MutPred		0.72		Gain of MoRF binding (P = 0.0084);.;.;
MVP		0.82
MPC		0.36
ClinPred		0.98	D
GERP RS		0.84
Varity_R		0.66
gMVP		0.024

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: chr19-21909930;