19-22391705-C-A

Variant names:

• chr19-22391705-C-A
• rs200235405
• NM_001098626.2:c.1530G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001098626.2(ZNF98):​c.1530G>T​(p.Met510Ile) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M510V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ZNF98 NM_001098626.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04458016).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098626.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF98	NM_001098626.2	MANE Select	c.1530G>T	p.Met510Ile	missense	Exon 4 of 4	NP_001092096.1	A6NK75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF98	ENST00000357774.9	TSL:1 MANE Select	c.1530G>T	p.Met510Ile	missense	Exon 4 of 4	ENSP00000350418.4	A6NK75

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149412 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149526 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73034

African (AFR) AF: 0.00 AC: 0 AN: 40770

American (AMR) AF: 0.00 AC: 0 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 4896

South Asian (SAS) AF: 0.00 AC: 0 AN: 4622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67076

Other (OTH) AF: 0.00 AC: 0 AN: 2074

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.61
DANN	Benign	0.38
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.015
Sift	Benign	0.50	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.070
MutPred		0.54		Gain of methylation at K509 (P = 0.0236)
MVP		0.13
MPC		0.96
ClinPred		0.021	T
GERP RS		0.069
Varity_R		0.046
gMVP		0.011
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs200235405; hg19: chr19-22574507; COSMIC: COSV63334228; COSMIC: COSV63334228;