chr19-21726693-A-T

Position:

• chr19-21726693-A-T

Variant summary

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

The NM_173531.4(ZNF100):​c.1619T>A​(p.Leu540Gln) 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. 14/20 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: ZNF100 NM_173531.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44

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=0.15785703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF100	NM_173531.4	c.1619T>A	p.Leu540Gln	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.1619T>A	p.Leu540Gln	missense_variant	5/5	1	NM_173531.4	ENSP00000351042.5
ZNF100	ENST00000305570.10	c.1427T>A	p.Leu476Gln	missense_variant	4/4	1		ENSP00000445201.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Aug 26, 2022

The c.1619T>A (p.L540Q) alteration is located in exon 5 (coding exon 5) of the ZNF100 gene. This alteration results from a T to A substitution at nucleotide position 1619, causing the leucine (L) at amino acid position 540 to be replaced by a glutamine (Q). 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	0.058
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.0044	T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.018	N
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
PROVEAN	Benign	0.25	N;.
REVEL	Benign	0.042
Sift	Uncertain	0.0020	D;.
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.97	D;.
Vest4		0.24
MutPred		0.51		Gain of solvent accessibility (P = 0.0074);.;
MVP		0.14
MPC		0.061
ClinPred		0.25	T
GERP RS		0.87
Varity_R		0.11
gMVP		0.042

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: chr19-21909495;