19-22391950-T-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001098626.2(ZNF98):c.1285A>T(p.Thr429Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000048 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0000035 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF98 NM_001098626.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.799

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.117156506).
• BP6: Variant 19-22391950-T-A is Benign according to our data. Variant chr19-22391950-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2396550.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF98	NM_001098626.2	c.1285A>T	p.Thr429Ser	missense_variant	4/4	ENST00000357774.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF98	ENST00000357774.9	c.1285A>T	p.Thr429Ser	missense_variant	4/4	1	NM_001098626.2	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 6 AN: 123716 Hom.: 0 Cov.: 20 FAILED QC

Gnomad AFR AF: 0.0000891

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000860

Gnomad ASJ AF: 0.000345

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000172

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000354 AC: 5 AN: 1411550 Hom.: 0 Cov.: 33 AF XY: 0.00000429 AC XY: 3 AN XY: 699718

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000370

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000485 AC: 6 AN: 123826 Hom.: 0 Cov.: 20 AF XY: 0.0000505 AC XY: 3 AN XY: 59440

Gnomad4 AFR AF: 0.0000888

Gnomad4 AMR AF: 0.0000859

Gnomad4 ASJ AF: 0.000345

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000172

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00135 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 05, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	10
Dann	Benign	0.39
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.063	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.085	N
MutationTaster	Benign	0.98	N
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.067
Sift	Benign	0.085	T
Sift4G	Benign	0.072	T
Polyphen		0.0050	B
Vest4		0.10
MutPred		0.48		Gain of MoRF binding (P = 0.126);
MVP		0.19
MPC		0.78
ClinPred		0.10	T
GERP RS		0.039
Varity_R		0.071
gMVP		0.0064

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: rs1477051261; hg19: chr19-22574752; COSMIC: COSV63337884; COSMIC: COSV63337884;