19-21726900-T-C

Position:

• chr19-21726900-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173531.4(ZNF100):​c.1412A>G​(p.Gln471Arg) 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. 13/20 in silico tools predict a benign outcome for this variant. 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: -1.18

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16812152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF100	NM_173531.4	c.1412A>G	p.Gln471Arg	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.1412A>G	p.Gln471Arg	missense_variant	5/5	1	NM_173531.4	ENSP00000351042.5
ZNF100	ENST00000305570.10	c.1220A>G	p.Gln407Arg	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

Dec 09, 2024

The c.1412A>G (p.Q471R) 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 1412, causing the glutamine (Q) at amino acid position 471 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	0.40
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.12
DANN	Benign	0.87
DEOGEN2	Benign	0.0011	T;.;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.000090	N
LIST_S2	Benign	0.019	.;.;T
M_CAP	Benign	0.00073	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.72	N;.;.
PROVEAN	Benign	-0.34	N;.;.
REVEL	Benign	0.022
Sift	Benign	0.40	T;.;.
Sift4G	Benign	0.56	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.096
MutPred		0.44		Gain of MoRF binding (P = 0.0145);.;.;
MVP		0.21
MPC		0.055
ClinPred		0.027	T
GERP RS		0.87
Varity_R		0.018
gMVP		0.0093

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: chr19-21909702;