19-22391930-T-A

Position:

• chr19-22391930-T-A

Variant summary

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

The NM_001098626.2(ZNF98):​c.1305A>T​(p.Lys435Asn) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 20)
• Consequence: ZNF98 NM_001098626.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.00

Genes affected

ZNF98 (HGNC:13174): (zinc finger protein 98) 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=0.20660746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF98	NM_001098626.2	c.1305A>T	p.Lys435Asn	missense_variant	4/4	ENST00000357774.9	NP_001092096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF98	ENST00000357774.9	c.1305A>T	p.Lys435Asn	missense_variant	4/4	1	NM_001098626.2	ENSP00000350418	P1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 20

Bravo AF: 0.00000378

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 09, 2021

The c.1305A>T (p.K435N) alteration is located in exon 4 (coding exon 4) of the ZNF98 gene. This alteration results from a A to T substitution at nucleotide position 1305, causing the lysine (K) at amino acid position 435 to be replaced by an asparagine (N). 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	0.51
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.0053	N
LIST_S2	Benign	0.015	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.10
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.012	D
Polyphen		0.98	D
Vest4		0.12
MutPred		0.36		Loss of methylation at K435 (P = 2e-04);
MVP		0.41
MPC		1.6
ClinPred		0.73	D
GERP RS		-0.13
Varity_R		0.18
gMVP		0.010

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

LitVar

Other links and lift over

dbSNP: rs1386129205; hg19: chr19-22574732;